Sambucus canadensis flowers
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Last updated 16 Sept 2023
Herbs, SARS, and CoVid-19: Summary
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Electron micrograph of SARS-CoV-2 (public domain image from CDC)
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Allium sativum (garlic)
In a double-blind trial, 66 non-immunocompromised Iranian adults with PCR-confirmed CoVid-19 pneumonia were randomized to either take allicin 90 mg/kg in three divided doses for 2 weeks or placebo (Yaghoubian, et al. 2021). All patients were given standard of care therapy appropriate to the time. The allicin extract was poorly characterized and was consistently also referred to as L-cysteine which makes little sense as these are distinct molecules (though allicin is synthesized from cysteine). There was a high drop-out rate (17 of those initially randomized), and an intention-to-treat analysis was not used. Cough, dyspnea, and myalgia were significantly reduced in the allicin vs. placebo group. Level of severity of pneumonia on chest CT scan was significantly reduced by allicin compared to placebo. Adverse effects were not reported. This preliminary study provides some support for use of garlic extracts in people with acute CoVid-19.
Allyl disulfide and trisulfide in particular, as well as many other organosulfur compounds in garlic steam-distilled volatile oil, interfere with SARS-CoV-2 binding to its ACE receptor and inhibits one of its proteases in vitro (Thuy, et al. 2020). There was clear synergy among the compounds in this model.
Garlic aqueous extract inhibited avian coronavirus IBV replication in chicken embryos (Mohajer Shojai, et al. 2016).
Two lectins derived from garlic were not effective at inhibiting SARS-CoV or feline infectious peritonitis virus (another coronavirus) in vitro (Keyaerts, et al. 2007). This is of relatively low interest as lectins are very poorly absorbed and thus unlikely to be relevant to treating systemic viral infections anyway.
Garlic is widely used traditionally to treat a range of upper and lower respiratory tract infections. Just one clinical trial has been conducted for preventing upper respiratory tract infections, and garlic showed efficacy (Josling 2001). Evidence is much more mixed on its utility to treat the common cold (Lissiman, et al. 2014).
Expert opinion: garlic is a safe food/medicine that has a reasonable chance of preventing and/or treating CoVid-19, but clinical trials are needed to confirm this.
Allyl disulfide and trisulfide in particular, as well as many other organosulfur compounds in garlic steam-distilled volatile oil, interfere with SARS-CoV-2 binding to its ACE receptor and inhibits one of its proteases in vitro (Thuy, et al. 2020). There was clear synergy among the compounds in this model.
Garlic aqueous extract inhibited avian coronavirus IBV replication in chicken embryos (Mohajer Shojai, et al. 2016).
Two lectins derived from garlic were not effective at inhibiting SARS-CoV or feline infectious peritonitis virus (another coronavirus) in vitro (Keyaerts, et al. 2007). This is of relatively low interest as lectins are very poorly absorbed and thus unlikely to be relevant to treating systemic viral infections anyway.
Garlic is widely used traditionally to treat a range of upper and lower respiratory tract infections. Just one clinical trial has been conducted for preventing upper respiratory tract infections, and garlic showed efficacy (Josling 2001). Evidence is much more mixed on its utility to treat the common cold (Lissiman, et al. 2014).
Expert opinion: garlic is a safe food/medicine that has a reasonable chance of preventing and/or treating CoVid-19, but clinical trials are needed to confirm this.
Andrographis paniculata (andrographis, 穿心蓮 chuān xīn lián)
In a quadruple blind (patients, caregivers, investigators, and outcomes assessors) clinical trial, 86 Georgian adults with mild CoVid-19 were randomized to take a combination of andrographis and Eleutherococcus senticosus (eleuthero) root or placebo (Ratiani, et al. 2022). The dose was 2 caps tid x 2 weeks. Each capsule contained 260 mg of andrographis extract standardized to 15 mg diterpene lactones and 18.75 mg of eleuthero extract standardized to 0.25 mg eleutherosides B and E. Significantly fewer patients taking the herbal formula deteriorated compared to placebo (10% vs 24%, number needed to treat to prevent one case progressing 7). The herbs also significantly improved viral clearance rate, duration of fever, and relief of sore throat, cough, myalgia, and other symptoms compared to placebo. There were no adverse effects reported in either group.
Another clinical trial, the details of which could not be obtained, apparently found that an andrographis extract at a dose of 180 mg qd for 5 d, reduced CoVid-19 symptom severity and duration more effectively than isolated andrographolide 60 mg qd or standard treatment (Rattanaraksa, et al. 2021). The only adverse effects were mild digestive upset.
A single-blind trial in 130 Chinese adults hospitalized with PCR-confirmed but mild CoVid-19 randomized them to standard of care alone or standard of care plus xi yan ping injection (Zhang, et al. 2021). This medicine contains two semi-synthetic compounds derived from andrographis, 9‐dehydro‐17‐hydro‐andrographolide and sodium 9‐dehydro‐17‐hydro‐andrographolide‐19‐yl sulfate 25 mg/ml. These are more water soluble and thus effective and safe for intravenous injection. Patients were treated with xi yan ping 10 mg/kg up to a maximum of 500 mg once daily for 7–14 days. Symptom duration was significantly shorter in those receiving the injections (average 8.3 vs 11.9 days), including when adjusted for age. Viral clearance was also significantly faster in the xi yan ping group compared to controls (average 8 vs 12.2 days). Six control patients deteriorated while none receiving xi yan ping did, a significant difference. Adverse effects were mild and did not differ between the groups.
See also the ImmuActive formula section below for discussion of a clinical trial involving a combination of compounds including andrographolide for CoVid-19.
A retrospective study in a hospital in Thailand reviewed 605 patients with PCR-confirmed CoVid-19, of whom 351 received andrographis within 5 days of admission (Tanwettiyanont, eta l. 2022). The product used contained 500 mg andrographis per capsule standardized to 20 mg andrographolide, and the dose was 3 caps bid x 5 days. There was no difference in rates of progression to pneumonia or worsening of symptoms in those who took andrographis compared to those who didn't. Why these results are so different from those of randomized clinical trials mentioned above is unknown, but clearly those trials are more robust. Adverse effects were not discussed.
One in silico study found that the constituent andrographolide would likely inhibit SARS-CoV-2's main protease (Enmozhi, et al. 2021). Another found that andrographolide and dihydroxydimethoxyflavone from andrographis bind the active site of SARS-CoV-2 main protease's active site more than hydroxychloroquine, nelfinavir, or remdesivir (Rajagopal, et al. 2020). A different flavonoid, 5,4'-dihydroxy-7-O-β -D-pyran-glycuronate butyl ester, and an andrographolide glycoside were also found to potently inhibit this protease in vitro (Sukardiman, et al. 2020). An analysis in human lung epithelial cells also found both andrographolide and a crude ethanol extract very active against the SARS-CoV-2 main protease (Sa-Ngiamsuntorn, et al. 2021). Another study found that andrographolide and andrographoside effectively inhibited SARS-CoV-2 3C-like protease in vitro (Zhu, et al. 2022).
Andrographolide inhibited SARS-CoV-2 spike protein and ACE2 receptor in vitro, suggesting a possible preventative benefit (Maurya, et al. 2020).
A computational analysis concluded that andrographolide had the best potential (of the molecules assessed, both synthetic and natural) to suppress the cytokine storm activated by SARS-CoV-2 infection (Rehan, et al. 2021). A review of mechanistic studies on andrographolide found it acts on many pathways believed to be involved in CoVid-19 cytokine storms, confirming the potential of andrographis in the treatment of people with this condition (Banerjee, et al. 2021).
Expert opinion: The majority of clinical trials support that this is effective for treating CoVid-19, particularly in patients with mild disease (though it may also be helpful in more severe cases).
Another clinical trial, the details of which could not be obtained, apparently found that an andrographis extract at a dose of 180 mg qd for 5 d, reduced CoVid-19 symptom severity and duration more effectively than isolated andrographolide 60 mg qd or standard treatment (Rattanaraksa, et al. 2021). The only adverse effects were mild digestive upset.
A single-blind trial in 130 Chinese adults hospitalized with PCR-confirmed but mild CoVid-19 randomized them to standard of care alone or standard of care plus xi yan ping injection (Zhang, et al. 2021). This medicine contains two semi-synthetic compounds derived from andrographis, 9‐dehydro‐17‐hydro‐andrographolide and sodium 9‐dehydro‐17‐hydro‐andrographolide‐19‐yl sulfate 25 mg/ml. These are more water soluble and thus effective and safe for intravenous injection. Patients were treated with xi yan ping 10 mg/kg up to a maximum of 500 mg once daily for 7–14 days. Symptom duration was significantly shorter in those receiving the injections (average 8.3 vs 11.9 days), including when adjusted for age. Viral clearance was also significantly faster in the xi yan ping group compared to controls (average 8 vs 12.2 days). Six control patients deteriorated while none receiving xi yan ping did, a significant difference. Adverse effects were mild and did not differ between the groups.
See also the ImmuActive formula section below for discussion of a clinical trial involving a combination of compounds including andrographolide for CoVid-19.
A retrospective study in a hospital in Thailand reviewed 605 patients with PCR-confirmed CoVid-19, of whom 351 received andrographis within 5 days of admission (Tanwettiyanont, eta l. 2022). The product used contained 500 mg andrographis per capsule standardized to 20 mg andrographolide, and the dose was 3 caps bid x 5 days. There was no difference in rates of progression to pneumonia or worsening of symptoms in those who took andrographis compared to those who didn't. Why these results are so different from those of randomized clinical trials mentioned above is unknown, but clearly those trials are more robust. Adverse effects were not discussed.
One in silico study found that the constituent andrographolide would likely inhibit SARS-CoV-2's main protease (Enmozhi, et al. 2021). Another found that andrographolide and dihydroxydimethoxyflavone from andrographis bind the active site of SARS-CoV-2 main protease's active site more than hydroxychloroquine, nelfinavir, or remdesivir (Rajagopal, et al. 2020). A different flavonoid, 5,4'-dihydroxy-7-O-β -D-pyran-glycuronate butyl ester, and an andrographolide glycoside were also found to potently inhibit this protease in vitro (Sukardiman, et al. 2020). An analysis in human lung epithelial cells also found both andrographolide and a crude ethanol extract very active against the SARS-CoV-2 main protease (Sa-Ngiamsuntorn, et al. 2021). Another study found that andrographolide and andrographoside effectively inhibited SARS-CoV-2 3C-like protease in vitro (Zhu, et al. 2022).
Andrographolide inhibited SARS-CoV-2 spike protein and ACE2 receptor in vitro, suggesting a possible preventative benefit (Maurya, et al. 2020).
A computational analysis concluded that andrographolide had the best potential (of the molecules assessed, both synthetic and natural) to suppress the cytokine storm activated by SARS-CoV-2 infection (Rehan, et al. 2021). A review of mechanistic studies on andrographolide found it acts on many pathways believed to be involved in CoVid-19 cytokine storms, confirming the potential of andrographis in the treatment of people with this condition (Banerjee, et al. 2021).
Expert opinion: The majority of clinical trials support that this is effective for treating CoVid-19, particularly in patients with mild disease (though it may also be helpful in more severe cases).
Artemisia annua (sweet Annie, qīng hāo 靑蒿) and Artemisinins
A combination of constituents from sweet Annie inhibited SARS-CoV-2 replication (including B1.1.7 and B1.351 variants) in vitro, not just artemisinin (Nair, et al. 2021). Even 12+ year-old dried leaf was still active. However, semi-synthetic derivates of artemisinin artesunate, artemether, and dihydroartemisinin, were not active.
In a double-blind, randomized trial in 50 Israeli adults hospitalized with PCR-confirmed CoVid-19, were all treated with standard of care plus an oral spray containing artemisinin 6 mg, curcumin 20 mg, Boswellia spp (frankincense) 15 mg, and vitamin C 60 mg twice per day or placebo for 2 days (Hellou, et al. 2022). This trial had numerous problems including that the placebo was just water so it is hard to believe patients wouldn't know they weren't receiving treatment, all the doses of the treatment agents were absurdly low, the trial duration was very short, and frankincense is endangered and should not be used. Nevertheless, the herbal formula reported improved or stabilized clinical signs and symptoms significantly better than placebo. There was no difference in adverse effects between the groups.
In an open clinical trial, 41 Chinese adults with mild (no pneumonia)-to-moderate (pneumonia) PCR-confirmed CoVid-19 were treated with either artemisinin 125 mg and piperaquine 750 mg on the first day then artemisinin 62.5 mg and piperaquine 375 mg daily for the next 6 days or hydroxychloroquine 800 mg qd for 3 days then 400 mg qd fo 5 days plus umifenovir 200 mg tid for 8 days (Li, et al. 2021a). Umifenovir is an antiviral drug available in China and Russia. Group allocation was not randomized. Significantly more patients in the artemisinin + piperaquine group took herbal medicines of any kind during the trial than the control group by chance. The artemisinin + piperaquine group achieved undetectable viral loads significantly more quickly than controls. Average duration of hospitalization was 13.3 days with artemisinin + piperaquine vs. 21.3 days with hydroxychloroquine + umifenovir (statistical analysis not provided). Serum aminotransferases were significantly elevated in four patients on artemisinin + piperaquine, and the QT interval was prolonged in 17.
An open, randomized clinical trial in 186 South African adults with PCR-confirmed mild-to-moderate CoVid-19 were all treated with either acetaminophen alone or combined with artesunate-amodiaquine, pyronaridine-artesunate, favipiravir -nitazoxanide, or sofosbuvir-daclatasvir (Chandiwana, et al. 2022). None of the treatment groups achieved viral clearance any faster than the acetaminophen-long group, but all were well tolerated.
Expert opinion: A lot more work is needed to determine is artemisinin or any semi-synthetic derivatives of it, as well as crude sweet Annie, have any efficacy in treating people with CoVid-19. Clinical uses of these substances for these patients is not recommended until more definitive clinical trials are published.
In a double-blind, randomized trial in 50 Israeli adults hospitalized with PCR-confirmed CoVid-19, were all treated with standard of care plus an oral spray containing artemisinin 6 mg, curcumin 20 mg, Boswellia spp (frankincense) 15 mg, and vitamin C 60 mg twice per day or placebo for 2 days (Hellou, et al. 2022). This trial had numerous problems including that the placebo was just water so it is hard to believe patients wouldn't know they weren't receiving treatment, all the doses of the treatment agents were absurdly low, the trial duration was very short, and frankincense is endangered and should not be used. Nevertheless, the herbal formula reported improved or stabilized clinical signs and symptoms significantly better than placebo. There was no difference in adverse effects between the groups.
In an open clinical trial, 41 Chinese adults with mild (no pneumonia)-to-moderate (pneumonia) PCR-confirmed CoVid-19 were treated with either artemisinin 125 mg and piperaquine 750 mg on the first day then artemisinin 62.5 mg and piperaquine 375 mg daily for the next 6 days or hydroxychloroquine 800 mg qd for 3 days then 400 mg qd fo 5 days plus umifenovir 200 mg tid for 8 days (Li, et al. 2021a). Umifenovir is an antiviral drug available in China and Russia. Group allocation was not randomized. Significantly more patients in the artemisinin + piperaquine group took herbal medicines of any kind during the trial than the control group by chance. The artemisinin + piperaquine group achieved undetectable viral loads significantly more quickly than controls. Average duration of hospitalization was 13.3 days with artemisinin + piperaquine vs. 21.3 days with hydroxychloroquine + umifenovir (statistical analysis not provided). Serum aminotransferases were significantly elevated in four patients on artemisinin + piperaquine, and the QT interval was prolonged in 17.
An open, randomized clinical trial in 186 South African adults with PCR-confirmed mild-to-moderate CoVid-19 were all treated with either acetaminophen alone or combined with artesunate-amodiaquine, pyronaridine-artesunate, favipiravir -nitazoxanide, or sofosbuvir-daclatasvir (Chandiwana, et al. 2022). None of the treatment groups achieved viral clearance any faster than the acetaminophen-long group, but all were well tolerated.
Expert opinion: A lot more work is needed to determine is artemisinin or any semi-synthetic derivatives of it, as well as crude sweet Annie, have any efficacy in treating people with CoVid-19. Clinical uses of these substances for these patients is not recommended until more definitive clinical trials are published.
Astragalus propinquus (astragalus, 黃蓍 huáng qí)
Formerly called Astragalus membranaceus, this is a major traditional antiviral and respiratory tract immunomodulator.
This was part of many traditional Chinese herbal formulas used to treat SARS in randomized trials; one meta-analysis found such formulas reduced symptoms and corticosteroid use without reducing mortality (Liu, et al. 2012).
Inhibits replication of, and cytokine production stimulation by, avian coronavirus IBV in vitro (Zhang, et al. 2018).
Enhances efficacy of anti-IBV vaccine in chickens (Zhang, et al. 2017; Qiu, et al. 2007).
Expert opinion: This herb has strong potential to help prevent and treat CoVid-19, as well as to enhance the efficacy of vaccines against this disease. Prospective clinical trials are strongly warranted.
This was part of many traditional Chinese herbal formulas used to treat SARS in randomized trials; one meta-analysis found such formulas reduced symptoms and corticosteroid use without reducing mortality (Liu, et al. 2012).
Inhibits replication of, and cytokine production stimulation by, avian coronavirus IBV in vitro (Zhang, et al. 2018).
Enhances efficacy of anti-IBV vaccine in chickens (Zhang, et al. 2017; Qiu, et al. 2007).
Expert opinion: This herb has strong potential to help prevent and treat CoVid-19, as well as to enhance the efficacy of vaccines against this disease. Prospective clinical trials are strongly warranted.
Azadirachta indica (neem निंब)
A group of 154 Indian health care workers and relatives of people infected with CoVid-19 participated in a double-blind, randomized trial (Nesari, et al. 2021). A proprietary extract (details not provided, except apparently nimbolide, nimbin, and salannin markers were standardized) of neem leaf extract made by Nisarga Biotech 50 mg bid or placebo for 1 month, and followed for an additional month after completion of the trial. More participants receiving placebo tested positive for CoVid-19 than those taking neem extract, but no statistical analysis was provided. Rates of adverse effects appeared the same between the groups, but again, no statistical analysis was provided to confirm this.
Ethyl acetate fractions of methanol extracts of neem leaves inhibited SARS-CoV-2 in vitro, with an IC50 of 8.5 mcg/ml (Hemdan, et al. 2023). The neem compound nimbin, a triterpenoid, inhibited SARS-CoV-2 spike protein and ACE2 receptor in vitro (Maurya, et al. 2020). In vitro, nimbochalcin, melianin B and vepaol from neem were shown to inhibit TMPRSS2, a critical receptor involved in CoVid-19 infection (Senapati, et al. 2021). Several compounds from neem were shown to inhibit SARS-CoV-2 chymotrypsin-like main protease (3CLpro) in vitro (Adegbola, et al. 2021).
Expert opinion: Based on its traditional use and efficacy for a wide range of other evidence that neem is active against many pathogens, this is certainly logical to use in CoVid-19. The one otherwise promising trial was largely invalidated by failure to provide a statistical analysis.
Ethyl acetate fractions of methanol extracts of neem leaves inhibited SARS-CoV-2 in vitro, with an IC50 of 8.5 mcg/ml (Hemdan, et al. 2023). The neem compound nimbin, a triterpenoid, inhibited SARS-CoV-2 spike protein and ACE2 receptor in vitro (Maurya, et al. 2020). In vitro, nimbochalcin, melianin B and vepaol from neem were shown to inhibit TMPRSS2, a critical receptor involved in CoVid-19 infection (Senapati, et al. 2021). Several compounds from neem were shown to inhibit SARS-CoV-2 chymotrypsin-like main protease (3CLpro) in vitro (Adegbola, et al. 2021).
Expert opinion: Based on its traditional use and efficacy for a wide range of other evidence that neem is active against many pathogens, this is certainly logical to use in CoVid-19. The one otherwise promising trial was largely invalidated by failure to provide a statistical analysis.
Berberine-Containing Herbs and Berberine
Coptis chinensis (goldthread, 黃連 huáng lián) inhibited murine coronavirus and porcine epidemic diarrhea virus replication in vitro (Kim, et al. 2008).
Phellodendron amurense (Amur cork, 黃栢 huáng bǎi) inhibited murine coronavirus and porcine epidemic diarrhea virus replication in vitro (Kim, et al. 2008).
Berberine inhibits SARS-CoV-2 replication in vitro (Pizzorno, et al. 2020). However, it antagonized remdesivir in this model. Berberine is somewhat notorious for binding to and interfering with some drugs, so caution is warranted with this combination until human research can be done. If used together, berberine and remdesivir should be administered at separate times of day.
Berberine inhibited SARS-CoV-2 spike protein and ACE2 receptor in vitro, suggesting a possible preventative benefit (Maurya, et al. 2020).
Berberine showed excellent, high-affinity, in-silico docking with SARS-CoV-2 protease (Narkhede, et al. 2020).
Expert opinion: It is not clear how much berberine actually makes it to the lungs or anywhere else targeted by CoVid-19 except the gut. More research is needed before berberine-containing herbs can be recommended for this disease.
Phellodendron amurense (Amur cork, 黃栢 huáng bǎi) inhibited murine coronavirus and porcine epidemic diarrhea virus replication in vitro (Kim, et al. 2008).
Berberine inhibits SARS-CoV-2 replication in vitro (Pizzorno, et al. 2020). However, it antagonized remdesivir in this model. Berberine is somewhat notorious for binding to and interfering with some drugs, so caution is warranted with this combination until human research can be done. If used together, berberine and remdesivir should be administered at separate times of day.
Berberine inhibited SARS-CoV-2 spike protein and ACE2 receptor in vitro, suggesting a possible preventative benefit (Maurya, et al. 2020).
Berberine showed excellent, high-affinity, in-silico docking with SARS-CoV-2 protease (Narkhede, et al. 2020).
Expert opinion: It is not clear how much berberine actually makes it to the lungs or anywhere else targeted by CoVid-19 except the gut. More research is needed before berberine-containing herbs can be recommended for this disease.
Curcuma longa (turmeric) and curcumin
A meta-analysis of six clinical trials found that curcumin significantly reduced symptoms, duration of hospitalization, and mortality in patients with CoVid-19 (Vahedian-Azimi, et al. 2022). This was associated with effective reduction of inflammatory cytokines while increasing anti-inflammatory cytokine levels.
In a double-blind, randomized trial, 140 Indian hospitalized adults with CoVid-19 (of mild, moderate, or severe severity) compared curcumin 525 mg with 2.5 mg piperine to a Bacillus spp probiotic, both given twice daily for 14 days (Pawar, et al. 2021). In the group with mild symptoms, curcumin + piperine led to significantly more patients maintaining an oxygen saturation >94% on room air, significantly fewer patients requiring oxygen, and stability of serum CRP and D-dimer levels, all compared to controls. In the moderate-severity group, curcumin + piperine led to significantly more patients maintaining an oxygen saturation >94% on room air, fewer with a CRP rise, less requirement for prone positioning to improve respiration, and less use of heparin and remdesivir compared to controls. In the group with severe symptoms, curcumin + piperine led to significantly fewer patients needing oxygen via high-flow nasal cannulas, fewer patients hospitalized for 10 or more days, and significantly less pulmonary fibrosis compared to controls. No statistical analysis was provided for two of the outcome measures (one primary [days to remission of symptoms] and one secondary [duration of ventilator assistance]), both listed as the first among all the outcomes, with no explanation provided as to why. There were fewer deaths with curcumin + piperine (2/15) in the severe group compared to the placebo group (5/15), with no statistical analysis of this difference provided.
A randomized, double-blind trial in 40 Iranian adults with CoVid-19 found that nano-curcumin 40 mg qid for 14 days lowered serum IL-1β and IL-6 expression compared to a placebo control (Valizadeh, et al. 2020). This same product at the same dose was tested in another randomized, double-blind trial compared to placebo in 40 hospitalized Iranian adults with mostly moderate or severe CoVid-19 (Hassaniazad, et al. 2021). This study also lasted 14 days. The nano-curcumin product did not lead to any clinically or statistically significant improvements in clinical status compared to placebo. A similar double-blind trial on the same product randomized 60 Iranian adults with mild-to-moderate CoVid-19 to 80 mg bid for 14 days (Ahmadi, et al. 2021). All participants were taking a range of other treatments. Time to resolution of cough, chills, myalgia, and smell and taste disturbance was significantly shorter with nano-curcumin compared to placebo. Lymphocyte count was significantly higher with nano-curcumin compared to placebo. There were no adverse effects associated with nano-curcumin.
See the ImmuActive trial below for a clinical study on this curcumin-containing formula.
In an open trial in 50 Pakistani outpatients with mild, PCR-confirmed CoVid-19, all received acetaminophen and sometimes azithromycin, and some were randomly assigned to also receive curcumin 168 mg, quercetin 260 mg, and vitamin D3 9 µg (360 IU) bid (Khan, et al. 2022). Even with these very low doses, CoVid-19 infection cleared (based on PCR results) significantly more quickly with the supplements than without. Symptomatic improvement showed only a statistical trend toward improving more quickly with the supplements than without. A very similar open trial in 50 Pakistani outpatients compared just curcumin 168 mg and quercetin 260 mg bid (without vitamin D) to standard of care alone and found similar results (Ujjan, et al. 2023).
Curcumin inhibits SARS-CoV-2 spike protein and ACE2 receptor in vitro (Maurya, et al. 2020). This suggests it could have preventative value against CoVid-19. In silico, cyclocurcumin and curcumin bind the active site of SARS-CoV-2 main protease's active site more than hydroxychloroquine, nelfinavir, or remdesivir (Rajagopal, et al. 2020).
Curcumin was a potent inhibitor of SARS-CoV in vitro when applied to the cells prior to infection (Wen, et al. 2007).
Curcumin potently inhibits the coronavirus, transmissible gastroenteritis virus, in vitro (Li, et al. 2020b).
Evidence from non-coronavirus studies suggest curcumin would inhibit cytokine storms (Liu and Ying 2020).
Expert opinion: Curcumin is one of the most studied groups of herbal compounds in people with CoVid-19 infections and shows ongoing promise in these clinical trials. Focusing on curcumin alone, ignoring all the other constituents in turmeric, is likely a mistake, and future trials should investigate whole turmeric in head-to-head trials with curcumin.
In a double-blind, randomized trial, 140 Indian hospitalized adults with CoVid-19 (of mild, moderate, or severe severity) compared curcumin 525 mg with 2.5 mg piperine to a Bacillus spp probiotic, both given twice daily for 14 days (Pawar, et al. 2021). In the group with mild symptoms, curcumin + piperine led to significantly more patients maintaining an oxygen saturation >94% on room air, significantly fewer patients requiring oxygen, and stability of serum CRP and D-dimer levels, all compared to controls. In the moderate-severity group, curcumin + piperine led to significantly more patients maintaining an oxygen saturation >94% on room air, fewer with a CRP rise, less requirement for prone positioning to improve respiration, and less use of heparin and remdesivir compared to controls. In the group with severe symptoms, curcumin + piperine led to significantly fewer patients needing oxygen via high-flow nasal cannulas, fewer patients hospitalized for 10 or more days, and significantly less pulmonary fibrosis compared to controls. No statistical analysis was provided for two of the outcome measures (one primary [days to remission of symptoms] and one secondary [duration of ventilator assistance]), both listed as the first among all the outcomes, with no explanation provided as to why. There were fewer deaths with curcumin + piperine (2/15) in the severe group compared to the placebo group (5/15), with no statistical analysis of this difference provided.
A randomized, double-blind trial in 40 Iranian adults with CoVid-19 found that nano-curcumin 40 mg qid for 14 days lowered serum IL-1β and IL-6 expression compared to a placebo control (Valizadeh, et al. 2020). This same product at the same dose was tested in another randomized, double-blind trial compared to placebo in 40 hospitalized Iranian adults with mostly moderate or severe CoVid-19 (Hassaniazad, et al. 2021). This study also lasted 14 days. The nano-curcumin product did not lead to any clinically or statistically significant improvements in clinical status compared to placebo. A similar double-blind trial on the same product randomized 60 Iranian adults with mild-to-moderate CoVid-19 to 80 mg bid for 14 days (Ahmadi, et al. 2021). All participants were taking a range of other treatments. Time to resolution of cough, chills, myalgia, and smell and taste disturbance was significantly shorter with nano-curcumin compared to placebo. Lymphocyte count was significantly higher with nano-curcumin compared to placebo. There were no adverse effects associated with nano-curcumin.
See the ImmuActive trial below for a clinical study on this curcumin-containing formula.
In an open trial in 50 Pakistani outpatients with mild, PCR-confirmed CoVid-19, all received acetaminophen and sometimes azithromycin, and some were randomly assigned to also receive curcumin 168 mg, quercetin 260 mg, and vitamin D3 9 µg (360 IU) bid (Khan, et al. 2022). Even with these very low doses, CoVid-19 infection cleared (based on PCR results) significantly more quickly with the supplements than without. Symptomatic improvement showed only a statistical trend toward improving more quickly with the supplements than without. A very similar open trial in 50 Pakistani outpatients compared just curcumin 168 mg and quercetin 260 mg bid (without vitamin D) to standard of care alone and found similar results (Ujjan, et al. 2023).
Curcumin inhibits SARS-CoV-2 spike protein and ACE2 receptor in vitro (Maurya, et al. 2020). This suggests it could have preventative value against CoVid-19. In silico, cyclocurcumin and curcumin bind the active site of SARS-CoV-2 main protease's active site more than hydroxychloroquine, nelfinavir, or remdesivir (Rajagopal, et al. 2020).
Curcumin was a potent inhibitor of SARS-CoV in vitro when applied to the cells prior to infection (Wen, et al. 2007).
Curcumin potently inhibits the coronavirus, transmissible gastroenteritis virus, in vitro (Li, et al. 2020b).
Evidence from non-coronavirus studies suggest curcumin would inhibit cytokine storms (Liu and Ying 2020).
Expert opinion: Curcumin is one of the most studied groups of herbal compounds in people with CoVid-19 infections and shows ongoing promise in these clinical trials. Focusing on curcumin alone, ignoring all the other constituents in turmeric, is likely a mistake, and future trials should investigate whole turmeric in head-to-head trials with curcumin.
Echinacea spp (purple coneflower)
See the clinical trial discussed under Zingiber officinale (ginger) and echinacea below.
A systematic review of prior trials found that various species of echinacea inhibit production of most pro-inflammatory cytokines (the one exception is IL-10 which appears to be upregulated by them) (Aucoin, et al. 2021). This supports the clinical observation that echinacea species do not cause increases in cytokine storm-type events in patients; quite the opposite.
A hydroethanolic extract of mostly the aerial parts of Echinacea purpurea (and a little bit of root) was shown to be virucidal against SARS-CoV-2, SARS-CoV, MERS, HCoV-229E (which causes the common cold), and yellow fever viruses in vitro (Signer, et al. 2020). All these are enveloped RNA viruses; no activity against DNA viruses was detected in this study. The IC50 was 3.2 mcg/ml against HCoV-229E. Total inhibition of all four coronaviruses studied occurred at a concentration of 50 mcg/ml.
See the discussion under Ligusticum spp below regarding the safe use of combination tinctures containing E. purpurea and E. angustifolia in people with CoVid-19 in a retrospective chart review.
Expert opinion: Echinacea species are safe to use in people with CoVid-19 and has significant potential to help in treatment (and prevention) of this disease. Robust clinical trials are warranted.
A systematic review of prior trials found that various species of echinacea inhibit production of most pro-inflammatory cytokines (the one exception is IL-10 which appears to be upregulated by them) (Aucoin, et al. 2021). This supports the clinical observation that echinacea species do not cause increases in cytokine storm-type events in patients; quite the opposite.
A hydroethanolic extract of mostly the aerial parts of Echinacea purpurea (and a little bit of root) was shown to be virucidal against SARS-CoV-2, SARS-CoV, MERS, HCoV-229E (which causes the common cold), and yellow fever viruses in vitro (Signer, et al. 2020). All these are enveloped RNA viruses; no activity against DNA viruses was detected in this study. The IC50 was 3.2 mcg/ml against HCoV-229E. Total inhibition of all four coronaviruses studied occurred at a concentration of 50 mcg/ml.
See the discussion under Ligusticum spp below regarding the safe use of combination tinctures containing E. purpurea and E. angustifolia in people with CoVid-19 in a retrospective chart review.
Expert opinion: Echinacea species are safe to use in people with CoVid-19 and has significant potential to help in treatment (and prevention) of this disease. Robust clinical trials are warranted.
Eleutherococcus senticosus (eleuthero)
See Andrographis paniculata above for a clinical trial combining these two herbs.
Glycyrrhiza glabra (licorice),
Glycyrrhiza uralensis and Glycyrrhiza inflata (甘草 gān cǎo)
Glycyrrhizin, a triterpenoid glycoside from the roots of all three of these species of Glycyrrhiza, inhibits SARS-CoV both before and after cellular infection in vitro at extremely low concentrations (Cinatl, et al. 2003; Chen, et al. 2004; Hoever, et al. 2005). Well above these concentrations can be achieved in humans with oral dosing of 600 mg of glycyrrhizin, which is a dose that will cause hypertension and other serious problems in most people if used for more than 2 weeks continuously (Glavač and Kreft 2012). Whether lower doses will work is unclear but likely, given synergy with other constituents in the herbs.
Many other preclinical studies have identified a range of ways licorice and its constituents could help treat CoVid-19, both due to direct effects on the virus and various ways it could alter host responses to it (Al-Kamel and Grundmann 2021; Chrzanowski, et al. 2021; Li, et al. 2021b; Bailly and Vergoten 2020; Chen, et al. 2020a; Luo, et al. 2020; Murck 2020). Glycyrrhizin showed excellent, high-affinity, in-silico docking with SARS-CoV-2 main protease (Narkhede, et al. 2020). An aqueous extract of licorice inhibited SARS-CoV-2 in vitro, as did glycyrrhizin at an EC50 of mg/ml (van de Sand, et al. 2021). Glycyrrhizin was the most potent and safe of many constituents at inhibiting SARS-CoV-2, particularly the spike protein and its binding to ACE2 (Yu, et al. 2020). Glycyrrhizic acid (the triterpenoid aglycone of glycyrrhizin) and liquiritin (a flavonoid) were strong inhibitors of SARS-CoV-2 3C-like protease in vitro (Zhu, et al. 2022).
Empirically, this is one of the most common herbs used in China during the CoVid-19 pandemic (Yang, et al. 2020). At least one case study found that glycyrrhizin and vitamin C were effective in one patient with severe CoVid-19 (Ding, et al. 2020). A retrospective analysis of 317 Chinese CoVid-19 patients found that glycyrrhizin, corticosteroids, thymosin, and immunoglobulins were associated with an increased risk of death (Wang, et al. 2021b). Given that a meta-analysis of prospective trials has found that corticosteroids at least clearly reduce risk of death from severe CoVid-19, not much weight can be given to such an analysis (WHO REACT, et al. 2020). Other retrospective series have found glycyrrhizin safe and effective for people with CoVid-19, such as one that combined it in many cases with the herbal formula 甘露消毒丹 gān lù xiāo dú dān (Sweet Dew Special Pill to Eliminate Toxin) (Chen, et al. 2020b). Another specifically found that glycyrrhizin could lower elevated serum transaminases safely in people with CoVid-19 (Liao, et al. 2021).
Glycyrrhizin had many benefits in people with SARS and MERS, the two prior epidemics caused by novel coronaviruses based on retrospective cohort studies (Li, et al. 2020a).
Expert opinion: Licorice is most likely useful in relatively high doses for treatment of SARS-CoV-2 infections for short periods of time, though lower doses may be preventative. Human clinical trials are urgently needed. Other analyses have come to largely the same conclusion (Silveira, et al. 2020).
Many other preclinical studies have identified a range of ways licorice and its constituents could help treat CoVid-19, both due to direct effects on the virus and various ways it could alter host responses to it (Al-Kamel and Grundmann 2021; Chrzanowski, et al. 2021; Li, et al. 2021b; Bailly and Vergoten 2020; Chen, et al. 2020a; Luo, et al. 2020; Murck 2020). Glycyrrhizin showed excellent, high-affinity, in-silico docking with SARS-CoV-2 main protease (Narkhede, et al. 2020). An aqueous extract of licorice inhibited SARS-CoV-2 in vitro, as did glycyrrhizin at an EC50 of mg/ml (van de Sand, et al. 2021). Glycyrrhizin was the most potent and safe of many constituents at inhibiting SARS-CoV-2, particularly the spike protein and its binding to ACE2 (Yu, et al. 2020). Glycyrrhizic acid (the triterpenoid aglycone of glycyrrhizin) and liquiritin (a flavonoid) were strong inhibitors of SARS-CoV-2 3C-like protease in vitro (Zhu, et al. 2022).
Empirically, this is one of the most common herbs used in China during the CoVid-19 pandemic (Yang, et al. 2020). At least one case study found that glycyrrhizin and vitamin C were effective in one patient with severe CoVid-19 (Ding, et al. 2020). A retrospective analysis of 317 Chinese CoVid-19 patients found that glycyrrhizin, corticosteroids, thymosin, and immunoglobulins were associated with an increased risk of death (Wang, et al. 2021b). Given that a meta-analysis of prospective trials has found that corticosteroids at least clearly reduce risk of death from severe CoVid-19, not much weight can be given to such an analysis (WHO REACT, et al. 2020). Other retrospective series have found glycyrrhizin safe and effective for people with CoVid-19, such as one that combined it in many cases with the herbal formula 甘露消毒丹 gān lù xiāo dú dān (Sweet Dew Special Pill to Eliminate Toxin) (Chen, et al. 2020b). Another specifically found that glycyrrhizin could lower elevated serum transaminases safely in people with CoVid-19 (Liao, et al. 2021).
Glycyrrhizin had many benefits in people with SARS and MERS, the two prior epidemics caused by novel coronaviruses based on retrospective cohort studies (Li, et al. 2020a).
Expert opinion: Licorice is most likely useful in relatively high doses for treatment of SARS-CoV-2 infections for short periods of time, though lower doses may be preventative. Human clinical trials are urgently needed. Other analyses have come to largely the same conclusion (Silveira, et al. 2020).
Hong Kong Formula for Prevention
A large, non-randomized, open clinical trial was conducted during the SARS epidemic among hospital staff (medical and non-medical personnel) in Hong Kong (Lau, et al. 2005). A total of 1,063 hospital staff volunteered to take an herbal formula designed to prevent SARS infection (see table below), while 15,374 controls chose not to rake it. The formula was created for this purpose; it was not a traditional formula (but was based on combining two traditional formulas then adding two additional herbs) and was not formally named. The ratio of herbs in the formula, the dose form (beyond "sachet" suggesting it was a powder or granulation), and the dose (beyond "one sachet per day") used were, frustratingly, not stated. The formulas was taken for two weeks. Of those who took the formula, none developed SARS. Of those who didn't take the formula, 64 (0.4%) developed SARS. This different was statistically significant in favor of the herbal formula have a preventative effect. A total of 19 (1.8%) of those who took the formula reported adverse effects, all of which were mild. Nine (0.8%) patients did elect to stop taking the formula because of their adverse effects. Given the very close similarity of the SARS-CoV and SARS-CoV-2 viruses, it is reasonable to consider use of this formula in the CoVid-19 pandemic among those at high risk of contracting the infection, particularly health care workers, the elderly, and people with pre-existing medical conditions that put them at risk.
|
Latin |
Part |
English |
Chinese |
|
Morus alba |
leaf |
white mulberry |
桑葉 sāng yè |
|
Chrysanthemum morifolium |
flower |
chrysanthemum |
菊花 jú huā |
|
Prunus armeniaca |
seed |
bitter apricot |
杏仁 xìng rén |
|
Forsythia suspensa |
fruit |
forsythia |
連翹 lián qiào |
|
Mentha haplocalyx |
leaf |
wild mint |
薄荷 bò hé |
|
Platycodon grandiflorum |
root |
balloon flower |
桔梗 jié gěng |
|
Glycyrrhiza uralensis |
root |
Chinese licorice |
甘草 gān cǎo |
|
Phragmites australis |
rhizome |
reed |
蘆根 lú gēn |
|
Astragalus propinquus |
root |
astragalus |
黃蓍 huáng qí |
|
Saposhnikovia divaricata |
root |
saposhnikovia |
防風 fáng fēng |
|
Isatis tinctoria |
leaf |
woad |
板藍根 bǎn lán gēn |
|
Scutellaria baicalensis |
root |
Baical skullcap |
黃芩 huáng qín |
It is recommend to compound the formula as either granulations (and take 5 g reconstituted in hot water qd cc) or as a tea (and use 10 g to infuse/decoct and drink one cup qd cc).
Houttuynia cordata (houttuynia, 魚腥草 yú xīng cǎo)
Protects chickens from getting avian coronavirus IBV infections (Yin, et al. 2011).
Leaf extract inhibits murine coronavirus infectivity for days (Chiow, et al. 2016). Total extract was more potent than isolated flavonoids or mixtures of just flavonoids extracted from the plant.
Inhibits coronavirus protease and RNA polymerase of SARS-CoV in vitro (Lau, et al. 2008).
Use of houttuynia had no effect on mortality, and was associated with prolonged hospitalization in an open trial that combined it with conventional medicine during the SARS epidemic (Li, et al. 2006).
Expert opinion: Do not use this herb alone with patients until additional clinical trials are done, given the concerning findings in the one open trial of this herb in SARS. Its use in combination formulas (including those reported above) found no harms and only benefit, so it may be used in this setting.
Leaf extract inhibits murine coronavirus infectivity for days (Chiow, et al. 2016). Total extract was more potent than isolated flavonoids or mixtures of just flavonoids extracted from the plant.
Inhibits coronavirus protease and RNA polymerase of SARS-CoV in vitro (Lau, et al. 2008).
Use of houttuynia had no effect on mortality, and was associated with prolonged hospitalization in an open trial that combined it with conventional medicine during the SARS epidemic (Li, et al. 2006).
Expert opinion: Do not use this herb alone with patients until additional clinical trials are done, given the concerning findings in the one open trial of this herb in SARS. Its use in combination formulas (including those reported above) found no harms and only benefit, so it may be used in this setting.
Humulus lupulus (hops)
A group of 50 Polish adults hospitalized with acute respiratory failure due to CoVid-19 were all treated with remdesivir, vitamin D3, dexamethasone, enoxaparin, and insulin (Dabrowski, et al. 2023). They were randomized to receive either xanthohumol from hops 1.5 mg/kg tid enterally or placebo in a double-blind fashion for 7 d. Significantly more patients survived to 28 d in the xanthohumol group than the control group, 80% vs. 52% respectively. All xanthohumol-treated patients who survived were ultimately discharged home in good condition; all control group members who lived were discharged to other pulmonary and/or rehab hospitals at 28 d with unknown long-term status (but not home in good condition). Significantly more control patients required prolonged (>7 d) mechanical ventilation compared to the xanthohumol group. The inflammatory markers IL-6 and D-dimer were significantly reduced by xanthohumol compared to the placebo group at day 7. There were no adverse effects attributable to xanthohumol.
Hyoscyamus niger (henbane)
Fifty Iranian adults with acute CoVid-19 pneumonia were randomized to either take placebo or a syrup containing 450 mg propolis/10 ml and 1.6 mg of a methanolic extract of Hyoscyamus niger (henbane), taken three times per day for six days in a double-blind, randomized trial (Kosari, et al. 2021). Cough, dyspnea, sore throat, fever, abdominal pain, myalgia, headache, dizziness, and diarrhea were all reduced significantly by the herbal syrup compared to placebo, while nausea and vomiting were not. There was no difference between the groups in terms of adverse effects.
Expert opinion: henbane and propolis are appropriate to include as part of a protocol for treating patients with CoVid-19 pneumonia. Henbane overdose can cause serious and even deadly anticholinergic syndrome and should only be used under the care of a clinician trained in the use of this powerful medicine.
Expert opinion: henbane and propolis are appropriate to include as part of a protocol for treating patients with CoVid-19 pneumonia. Henbane overdose can cause serious and even deadly anticholinergic syndrome and should only be used under the care of a clinician trained in the use of this powerful medicine.
ImmuActive Formula
This formula contains:
curcuminoids 100 mg
andrographolides 50 mg
resveratrol 50 mg
zinc monomethionine (elemental zinc 10 mg)
L-selenomethionine (elemental selenium 40 mcg)
piperine 3 mg
In a double-blind trial, 92 Indian adults with PCR-confirmed CoVid-19 who were hospitalized with mild disease or less severe were randomized to ImmuActive once daily or placebo (Majeed, et al. 2021). Treatment continued for 28 days or until transfer to the ICU, whichever came first. Disease severity decreased significantly in the treatment group compared to controls. It took an average of 1 day less to reduce disease severity with treatment compared to placebo. Significantly more patients were completely cured by the end of the study with ImmuActive compared to placebo, 42% vs. 23%. There were no adverse effects.
curcuminoids 100 mg
andrographolides 50 mg
resveratrol 50 mg
zinc monomethionine (elemental zinc 10 mg)
L-selenomethionine (elemental selenium 40 mcg)
piperine 3 mg
In a double-blind trial, 92 Indian adults with PCR-confirmed CoVid-19 who were hospitalized with mild disease or less severe were randomized to ImmuActive once daily or placebo (Majeed, et al. 2021). Treatment continued for 28 days or until transfer to the ICU, whichever came first. Disease severity decreased significantly in the treatment group compared to controls. It took an average of 1 day less to reduce disease severity with treatment compared to placebo. Significantly more patients were completely cured by the end of the study with ImmuActive compared to placebo, 42% vs. 23%. There were no adverse effects.
Lián Huā Qīng Qēn 连花清瘟
(Forsythia Flower to Clear the Plague)
for Treatment
An open, randomized clinical trial compared usual care to usual care plus this herbal formula (see table below) in 284 Chinese adults with symptomatic CoVid-19 pneumonia (Hu, et al. 2021). The dose of the formula was 4 caps tid, though the amount of material in each capsule was never disclosed (the website of the manufacturer, however, states that each capsule contains 350 mg). The trial ran for 14 days. Overall symptomatic recovery was significantly faster in the herbal formula group compared to controls, including specifically of fever, cough, and fatigue. The very low rates of conversion to severe CoVid-19 did not differ between the groups. There were no serious adverse effects, and no difference between the two groups in terms of overall adverse effects.
| Latin | Part | Chinese | English | Amount* |
| Forsythia suspensa | fruit | lián qiáo 連翹 | forsythia | 12.7% (170 g) |
| Lonicera japonica | flower bud | rěn dōng 忍冬 | Japanese honeysuckle | 12.7% (170 g) |
| shēng shí gāo 生石膏 | gypsum (calcium sulfate dihydrate) | 12.7% (170 g) | ||
| Isatis indigotica | root | sōng lán 菘藍 | woad | 12.7% (170 g) |
| Dryopteris crassirhizoma | rhizome | cū jīng lín máo jué 粗莖鱗毛蕨 | Thick-stemmed wood fern | 12.7% (170 g) |
| Houttuynia cordata | herb | yú xīng cǎo 魚腥草 | fish mint | 12.7% (170 g) |
| Ephedra sinica | stem | má huáng 麻黃 | Chinese ephedra | 4.2% (57 g) |
| Pogostemon cablin | herb | cāng zhú 蒼朮 | patchouli | 4.2% (57 g) |
| Glycyrrhiza uralensis | root | shēng gān cǎo 生甘草 | Chinese licorice | 4.2% (57 g) |
| Rhodiola crenulata | root | hóng jǐng tiān 紅景天 | Rose root | 4.2% (57 g) |
| Prunus sibirica | seed | shān xìng 山杏 | Siberian apricot | 4.2% (57 g) |
| Mentha haplocalyx | herb | bò hé 薄荷 | mint | menthol 0.4%** (57 g) |
| Rheum palmatum | root | zhǎng yè dà huáng掌葉大黃 | Chinese rhubarb | 2.5% (34 g) |
* The percentages listed are those given in the clinical trial, though no absolute amounts were given including the capsule size. The gram amounts listed after the percentages are the amounts given in the Chinese Pharmacopoeia.
** The product used in this trial used just pure menthol in the percentage given. The traditional formula contains the amount of mint given in grams.
** The product used in this trial used just pure menthol in the percentage given. The traditional formula contains the amount of mint given in grams.
Ligusticum spp (oshá),
Lomatium dissectum (lomatium), and
Osmorhiza occidentalis (western sweet cicely)
All these native western North American members of the Apiaceae family are strong traditional therapies for viral respiratory tract infections. They all appear to be broadly antiviral and immune stimulating, but have a built in inflammation-modulating effect so they do not cause an increase in cytokine storm or similar phenomena. This has been demonstrated in vitro using lomatium against influenza, and fits with the strong historical evidence that lomatium helps resolve influenza and does not cause worsening (Zamechek 2014).
In a retrospective chart review of 30 unselected patients with mild-to-moderate CoVid-19 seen at a rural naturopathic clinic in Oregon, a tincture was utilized in five that contained Ligusticum porteri (oshá) root, Inula helenium (elecampane) root, Echinacea purpurea/E. angustifolia (purple coneflower) aerial parts and root, and Berberis aquifolium (Oregon grape) root, equal parts of each, 0.5 tsp 5 x/d for 3–5 d, then ½ tsp tid for 3 more days (Barber, et al. 2021). Many other dietary supplements were also prescribed. Treatment was well tolerated and most had resolution of symptoms within 10 d; the only severe outcomes (notably hospitalization in one patient who did not take the tincture) were in patients who long delayed treatment after symptom onset and who had serious pre-existing conditions.
Expert opinion: These herbs are reasonable to include in protocols for people with CoVid-19 primary based on their traditional use for other respiratory infections and their excellent safety records. There is a small risk of any of these herbs causing a pruritic, self-limiting rash.
In a retrospective chart review of 30 unselected patients with mild-to-moderate CoVid-19 seen at a rural naturopathic clinic in Oregon, a tincture was utilized in five that contained Ligusticum porteri (oshá) root, Inula helenium (elecampane) root, Echinacea purpurea/E. angustifolia (purple coneflower) aerial parts and root, and Berberis aquifolium (Oregon grape) root, equal parts of each, 0.5 tsp 5 x/d for 3–5 d, then ½ tsp tid for 3 more days (Barber, et al. 2021). Many other dietary supplements were also prescribed. Treatment was well tolerated and most had resolution of symptoms within 10 d; the only severe outcomes (notably hospitalization in one patient who did not take the tincture) were in patients who long delayed treatment after symptom onset and who had serious pre-existing conditions.
Expert opinion: These herbs are reasonable to include in protocols for people with CoVid-19 primary based on their traditional use for other respiratory infections and their excellent safety records. There is a small risk of any of these herbs causing a pruritic, self-limiting rash.
Nigella sativa (black cumin)
In an open, randomized trial, 173 Saudi adults with acute, mild, PCR-confirmed CoVid-19 (non-pneumonia respiratory infections) were either given Nigella sativa oil 500 mg bid plus usual care or usual care for 10 days (Koshak 2021). The black cumin oil was cold-pressed and contained 0.7% thymoquinone. Results were analyzed on an intention to treat basis. The mean age of subjects was 36 yr. More subjects taking black cumin oil had recovered by day 14 post diagnosis compared to usual care only, and recovery time was significantly shorter than with usual care only. The only adverse effects were that three subjects taking black cumin oil had mild digestive upset. Four subjects in the control group were hospitalized for pneumonia compared to only one in the black cumin oil group (statistical analysis not provided). The trial protocol for this study was previously published (Koshak 2020).
Nigella sativa (black cumin) weakly inhibited murine coronavirus replication in vitro (Ulasli, et al. 2014).
Expert opinion: This appears to be reasonable for use in younger adult patients with mild disease, though data are limited. Studies are needed for patients with more severe disease. Black cumin oil is very safe.
Nigella sativa (black cumin) weakly inhibited murine coronavirus replication in vitro (Ulasli, et al. 2014).
Expert opinion: This appears to be reasonable for use in younger adult patients with mild disease, though data are limited. Studies are needed for patients with more severe disease. Black cumin oil is very safe.
Propolis
An open randomized trial in 124 Brazilian adults hospitalized with severe CoVid-19 disease compared standard of care at the time or the same plus either 400 mg or 800 mg per day of a dehydrated Brazilian green propolis extract (Duarte Silveira, et al. 2021). Mean hospital stay was significantly shorter (by 3--4 days) with either dose of propolis compared to the no-propolis group. There was no difference in duration in oxygen supplementation between the groups. The 800 mg propolis group had a significantly reduced risk of acute kidney injury compared to the control group. Adverse effects did not differ between the three groups.
See also the discussion of Hyoscyamus niger (henbane) above regarding the efficacy of a combination of propolis with that herb.
Expert opinion: Propolis is appropriate to include as part of a protocol for treating even serious CoVid-19 pneumonia.
See also the discussion of Hyoscyamus niger (henbane) above regarding the efficacy of a combination of propolis with that herb.
Expert opinion: Propolis is appropriate to include as part of a protocol for treating even serious CoVid-19 pneumonia.
Quercetin
See clinical trial combining this with curcumin under Curcuma longa above.
An open trial randomized 100 Pakistani adults with PCR-confirmed, early-stage, mild-to-moderate CoVid-19 to analgesics and antibiotics (as needed) alone to these drugs combined with quercetin phytosome 500 mg tid for 7 days followed by the same at a dose of 500 mg bid for 7 days (Di Perro, et al. 2022). The quercetin-treated group cleared the virus and their symptoms significantly more rapidly than the control group. One patient in the control group (who had diabetes mellitus, hypertension, and chronic kidney disease) was ultimately hospitalized and died; none in the quercetin group had such an outcome. There were no adverse effects of treatment.
An open trial randomized 100 Pakistani adults with PCR-confirmed, early-stage, mild-to-moderate CoVid-19 to analgesics and antibiotics (as needed) alone to these drugs combined with quercetin phytosome 500 mg tid for 7 days followed by the same at a dose of 500 mg bid for 7 days (Di Perro, et al. 2022). The quercetin-treated group cleared the virus and their symptoms significantly more rapidly than the control group. One patient in the control group (who had diabetes mellitus, hypertension, and chronic kidney disease) was ultimately hospitalized and died; none in the quercetin group had such an outcome. There were no adverse effects of treatment.
Qīng Fèi Pái Dú Táng 清肺排毒汤
(Clear the Lungs and Resolve Toxicity Decoction)
for Treatment
This massive formula contains 21 Chinese herbs. It is a combination based principally on four traditional Chinese herbal formulas, 麻杏石甘湯 Má Xìng Shí Gān Tāng (Ephedra, Apricot Kernel, Gypsum, and Licorice Decoction), 射干麻黃湯 Shè Gán Má Huáng Tāng (Belamcanda and Ephedra Decoction), 小柴胡湯丸 Xiǎo Chái Hú Tāng (Minor Bupleurum Decoction), and 五苓散丸 Wǔ Líng Sǎn (Powder of Five Types of Painful Urinary Dribbling) (Ren, et al. 2021). The ingredients are listed in the table below in order of amount (not in order of importance). Some sources list it as also containing Agastache rugosa or Morus alba. Potential mechanisms of actions of the herbs in this formula pertinent to CoVid-19 have been reviewed (Zhong, et al. 2020).
A meta-analysis has been published on 16 human trials of this formula for people with CoVid-19 pneumonia (Wang, et al. 2021a). Just one of these was a randomized controlled trial; two were cohort trials, six were open clinical trials, and seven were pre-post trials. Five trials (including the randomized trial) included a significant number (or only) patients that had severe or critical/life-threatening disease; the others either didn't report severity or included patients with mild-to-moderate severity. Dosing frequency and amount was extremely variable among the trials.
In-hospital mortality was half as much in those who took the formula compared to those who did not in this analysis. Hospital stay duration was significantly shortened by the formula in the randomized trial and those non-randomized trials that investigated this outcome compared to controls. Time to recover from symptoms was significantly shorter in thos who took the formula compared to those who didn't.
Adverse effects were rare and mild, mostly consistently of diarrhea, nausea and vomiting, or skin itching when they did occur.
Intriguingly, an open clinical trial not completed before the meta-analysis was published, found that using 1/30 the amounts of each herb in the formula as tea twice daily for 3 days in people with CoVid-19 led to significant increases in serum TNF‑α, IL‑1β, IL‑18, IL‑2, and and IL‑8 levels compared to baseline (Kageyama, et al. 2021). No adverse effects were associated with these effects. This suggests the formula restores early antiviral immunity that is often suppressed during CoVid-19 infection.
A randomized, placebo-controlled, double-blind trial of this formula is currently underway on this formula at UCLA.
A meta-analysis has been published on 16 human trials of this formula for people with CoVid-19 pneumonia (Wang, et al. 2021a). Just one of these was a randomized controlled trial; two were cohort trials, six were open clinical trials, and seven were pre-post trials. Five trials (including the randomized trial) included a significant number (or only) patients that had severe or critical/life-threatening disease; the others either didn't report severity or included patients with mild-to-moderate severity. Dosing frequency and amount was extremely variable among the trials.
In-hospital mortality was half as much in those who took the formula compared to those who did not in this analysis. Hospital stay duration was significantly shortened by the formula in the randomized trial and those non-randomized trials that investigated this outcome compared to controls. Time to recover from symptoms was significantly shorter in thos who took the formula compared to those who didn't.
Adverse effects were rare and mild, mostly consistently of diarrhea, nausea and vomiting, or skin itching when they did occur.
Intriguingly, an open clinical trial not completed before the meta-analysis was published, found that using 1/30 the amounts of each herb in the formula as tea twice daily for 3 days in people with CoVid-19 led to significant increases in serum TNF‑α, IL‑1β, IL‑18, IL‑2, and and IL‑8 levels compared to baseline (Kageyama, et al. 2021). No adverse effects were associated with these effects. This suggests the formula restores early antiviral immunity that is often suppressed during CoVid-19 infection.
A randomized, placebo-controlled, double-blind trial of this formula is currently underway on this formula at UCLA.
| Latin | Part | Chinese | English | Amount |
| shēng shí gāo 生石膏 | gypsum (calcium sulfate dihydrate) | 15–30 g | ||
| Bupleurum chinensis | root | chái hú 柴胡 | thorowax | 16 g |
| Wolfiporia cocos | sclerotium | fú líng 茯苓 | hoelen | 15 g |
| Dioscorea oppositifolia | rhizome | shān yào 山藥 | Chinese yam | 12 g |
| Ephedra sinica | stem | má huáng 麻黃 | Chinese ephedra | 9 g |
| Prunus armeniaca | seed | xìng rén 杏仁 | bitter almond | 9 g |
| Cinnamomum cassia | branch | guì zhī 桂枝 | cassia cinnamon | 9 g |
| Alisma plantago-aquatica | rhizome | zé xiè 澤瀉 | water plantain | 9 g |
| Polyporus umbellatus | fruiting body | zhū líng 豬苓 | lumpy bracket | 9 g |
| Atractylodes macrocephala | rhizome | bái zhú 白朮 | white atractylodes | 9 g |
| Pogostemon cablin | herb | guǎng huò xiāng 廣藿香 | Cablin patchouli | 9 g |
| Pinellia ternata | ginger-prepared rhizome | jiāng xià 薑夏 | pinellia | 9 g |
| Zingiber officinale | rhizome (fresh) | shēng jiāng 生薑 | ginger | 9 g |
| Aster tataricus | root | zǐ wǎn 紫菀 | purple aster | 9 g |
| Tussilago farfara | flower | kuǎn dōng huā 款冬花 | coltsfoot | 9 g |
| Iris domestica = Belamcanda chinensis | rhizome | shè gān 射干/td> | leopard lily | 9 g |
| Scutellaria baicalensis | root | huáng qín 黃芩 | Baikal skullcap | 6 g |
| Asarum heterotropoides var mandshuricum = Asarum sieboldii | herb | xì xīn 細辛 | Chinese wild ginger | 6 g |
| Citrus x aurantium | immature fruit | zhǐ shí 枳实 | bitter orange | 6 g |
| Citrus reticulata | aged peel | chén pí 陳皮 | tangerine | 6 g |
| Glycyrrhiza uralensis | baked root | zhì gán cǎo 炙甘草 | Chinese licorice | 6 g |
The recommended dose is 5–10 g three times per day of either the tea or the granules for 5–10 days maximum.
Rheum palmatum (rhubarb, 大黃 dà huáng)
|
Cooked root extracts and isolated compound emodin inhibit SARS-CoV protease (Luo, et al. 2009).
Emodin inhibits binding of SARS-CoV spike protein to ACE (Ho, et al. 2007). Emotion blocks 3a ion channel of SARS-CoV, which is necessary for the virus to bud out of the host cell (Schwarz, et al. 2011). Expert opinion: cooked root of rhubarb may have a role in CoVid-19 prevention and treatment, but clinical trials are needed. |
Emodin
|
Sambucus spp (Elder)
Sambucus cerulea habit
No research was identified on the effects of any species of Sambucus on SARS-CoV or SARS-CoV-2.
Sambucus nigra (black elder) fruit prevented cell entry by the avian coronavirus IBV in vitro (Chen, et al. 2014).
Sambucus javanica = S. formosana (Chinese elder) bark extract inhibited viral attachment and replication by the coronavirus HCOV-NL63 in vitro; caffeic and chlorogenic acids appeared to be mainly responsible (Weng, et al. 2019).
Though based on a selective review of the literature one could conclude that elder fruit might cause cytokine storms and worsen CoVid-19 infection, but clinical trials in people with influenza have not supported this idea, and in fact showed S. nigra (black elder) fruit was helpful in treating influenza without causing cytokine storms (Zakay-Rones, et al. 2004 and 1995).
Expert opinion: elder fruit and possibly the flowers are a safe medicine with some potential to prevent and/or treat CoVid-19, but clinical trials are needed to confirm this. They do not exacerbate or cause cytokine storms (quite the opposite!) in humans with viral infections.
Sambucus nigra (black elder) fruit prevented cell entry by the avian coronavirus IBV in vitro (Chen, et al. 2014).
Sambucus javanica = S. formosana (Chinese elder) bark extract inhibited viral attachment and replication by the coronavirus HCOV-NL63 in vitro; caffeic and chlorogenic acids appeared to be mainly responsible (Weng, et al. 2019).
Though based on a selective review of the literature one could conclude that elder fruit might cause cytokine storms and worsen CoVid-19 infection, but clinical trials in people with influenza have not supported this idea, and in fact showed S. nigra (black elder) fruit was helpful in treating influenza without causing cytokine storms (Zakay-Rones, et al. 2004 and 1995).
Expert opinion: elder fruit and possibly the flowers are a safe medicine with some potential to prevent and/or treat CoVid-19, but clinical trials are needed to confirm this. They do not exacerbate or cause cytokine storms (quite the opposite!) in humans with viral infections.
Scutellaria baicalensis (Baikal skullcap, 黃芩 huáng qín)
Scutellaria baicalensis flower (photo copyright E. Yarnell)
|
Studies in rats and mice found that 200 mg/kg of the flavonoid baicalein stopped body weight loss, inhibited SARS-CoV-2 replication, protected lung tissue against damage, improved respiratory function, and inhibited excessive inflammatory cytokine levels (Song, et al. 2021).
Three flavonoids from the root this plant, baicalein, scutellarein and ganhuangenin, were found to be the most potent inhibitors of SARS-CoV-2 3C-like protease in vitro of any of six Chinese herbal extracts or constituents from these extracts studied (Zhu, et al. 2022). In vitro, crude extract of Baikal skullcap and pure baicalein significantly inhibited SARS-CoV-2 replication and 3C-like protease activity (Liu, et al. 2021). Expert opinion: This has been part of several Chinese herbal formulas reported to have benefits in both preventing and treating CoVid-19. Given its extremely long history of safety, it is a plausible agent to use as part of the strategy for preventing and treating CoVid-19. More research is definitely warranted. |
Silybum marianum (milk thistle) and Silymarin
In a double-blind trial, 50 Iranian adults hospitalized with PCR-confirmed CoVid-19 requiring supplemental oxygen or mechanical ventilation, patients were randomized to silymarin nanomicelles 70 mg tid or placebo for 14 days (Aryan 2022). All patients received dexamethasone, remdesivir, oxygen therapy, and dextromethorphan. Serum ALT levels were significantly lower in the silymarin group compared to placebo 1 mon after treatment. All those treated with silymarin had normal ALT and AST levels 1 mon after treatment, compared to just 12 of 25 (48%) of the placebo group. Time to resolution of CoVid-19 symptoms and hospital stay duration were not significantly different between the groups. There were no obvious adverse effects from the silymarin nanomicelle product.
Expert opinion: It is unclear to what extent this outcome is valuable. The role of possible chronic hepatotoxicity in long CoVid-19 is undetermined. At present there are more effective and useful things to use in people with acute CoVid-19. Silymarin should be reserved for those with obvious and persistent hepatotoxicity.
Expert opinion: It is unclear to what extent this outcome is valuable. The role of possible chronic hepatotoxicity in long CoVid-19 is undetermined. At present there are more effective and useful things to use in people with acute CoVid-19. Silymarin should be reserved for those with obvious and persistent hepatotoxicity.
Xuān Fèi Bài Dú Táng 宣肺败毒汤
(Command the Lungs to Defeat Toxicity Decoction)
for Treatment
A formula combining 12 herbs and one mineral (see table) created by academician Boli Zhang Bo Li and Professor Liu Qing Quan in 2020 was studied in a prospective, open, randomized trial in adult Chinese patients with mild to severe acute CoVid-19 (Xiong, et al. 2020). All subjects (n=42) in the trial received conventional medical support appropriate to existing state guidelines; 22 of these also received the herbal formula. The dose was 200 ml of the herbal formula twice daily. Fever, cough, fatigue, and loss of appetite all resolved significantly more quickly in the herbal formula + conventional medicine group compared to conventional medicine only. White blood cells and lymphocytes improved significantly while C-reactive protein and erythrocyte sedimentation rate fell significantly in the herbal formula + conventional medicine group compared to conventional medicine only.
| Latin | Part | Chinese | English | Amount |
| Ephedra sinica | Stem | má huáng 麻黃 | Chinese ephedra | 8 g |
| Prunus armeniaca | Seed | xìng rén 杏仁 | bitter almond | 15 g |
| shēng shí gāo 生石膏 | gypsum (calcium sulfate dihydrate) | 30 g | ||
| Atractylodes chinensis | rhizome | cāng zhú 蒼朮 | black atractylodes | 10 g |
| Coix lachryma-jobi var ma-yuen | seed | yì yǐ rén 薏苡仁 | Job's tears | 30 g |
| Agastache rugosa | herb | huò xiāng 藿香 | licorice mint | 15 g |
| Falllopia japonica = Polygonum cuspidatum | rhizome, root | hǔ zhàng 虎杖 | Japanese knotweed | 20 g |
| Lepidium apetalum | seed | tíng lì zǐ 葶藶子 | pepperweed | 15 g |
| Verbena officinalis | herb | mǎ biān cǎo 馬鞭草 | European vervain | 30 g |
| Phragmites australis | rhizome | lú gēn 蘆根 | reed | 30 g |
| Artemisia annua | herb | qīng hāo 靑蒿 | sweet Annie | 25 g |
| Citrus reticulata | peel | jú hóng 橘紅 | red tangerine peel | 20 g |
| Glycyrrhiza uralensis | root | shēng gān cǎo 生甘草 | Chinese licorice | 10 g |
Zingiber officinale (ginger)
One open randomized trial involved 100 Iranian adults suspected of having CoVid-19 based on symptoms, chest X-ray findings, and the timing, this being early in the pandemic and thus widespread testing was not available (Mesri, et al. 2021). Participants were randomized to a combination of ginger tablets 1 g tid and echinacea tablets 1 tid. The species of Echinacea used and the amount in the tablet was not disclosed; the details of neither supplement were provided (in particular, were they crude, dried up and ground herb, or some kind of extract?). Everyone was treated with hydroxychloroquine (so basically controls received only this medication), which at the time was thought to be useful but has subsequently been shown ineffective for treating CoVid-19. The trial lasted 7 days.
The symptoms of cough, muscle pain, and dyspnea were alleviated significantly by the herbal combination compared to controls. Fever and sore throat were not different between the groups. Though only 2% of the herbal group ended up hospitalized compared to 6% of controls, this difference was not statistically significant. There were no adverse effects of the herbal treatment.
In another open randomized trial, 48 Indian outpatients with PCR-confirmed, mild-to-moderate CoVid-19 were treated with either ginger 500 mg and Withania somnifera (ashwagandha) 250 mg bid for 15 days combined with paracetamol, cetirizine, vitamin C, and/or azithromycin, or the drugs alone (Singh, et al. 2023). Virus and symptoms were cleared significantly more rapidly in the group that received ginger + ashwagandha compared to controls. There were no adverse effects.
Expert opinion: Though limited, these trials establish preliminary support for the safety of ginger, echinacea, and ashwagandha in people with mild-to-moderate CoVid-19, and suggests they may help reduce symptoms. These herbs are safe to use clinically now (though more frequent dosing is recommended for at least the first 2–3 days of being ill). Larger, double-blind trials with more clearly defined herbal interventions, and more frequent dosing of the herbs are clearly warranted.
The symptoms of cough, muscle pain, and dyspnea were alleviated significantly by the herbal combination compared to controls. Fever and sore throat were not different between the groups. Though only 2% of the herbal group ended up hospitalized compared to 6% of controls, this difference was not statistically significant. There were no adverse effects of the herbal treatment.
In another open randomized trial, 48 Indian outpatients with PCR-confirmed, mild-to-moderate CoVid-19 were treated with either ginger 500 mg and Withania somnifera (ashwagandha) 250 mg bid for 15 days combined with paracetamol, cetirizine, vitamin C, and/or azithromycin, or the drugs alone (Singh, et al. 2023). Virus and symptoms were cleared significantly more rapidly in the group that received ginger + ashwagandha compared to controls. There were no adverse effects.
Expert opinion: Though limited, these trials establish preliminary support for the safety of ginger, echinacea, and ashwagandha in people with mild-to-moderate CoVid-19, and suggests they may help reduce symptoms. These herbs are safe to use clinically now (though more frequent dosing is recommended for at least the first 2–3 days of being ill). Larger, double-blind trials with more clearly defined herbal interventions, and more frequent dosing of the herbs are clearly warranted.
Clinical Trials on Herbs for CoVid-19 in Progress
| Citation | Herb/Constituent | Dose form and dose | Population | Trial structure |
| Khan 2020 | Azadirachta indica leaf extract | Gargle and nasal lavage tid | Pakistanian adults with acute CoVid-19 | Double-blind randomized trial |
| Miryan 2020 | Curcumin + piperine | 1000 mg + 10 mg bid x 14 d | Iranian adults with mild or severe acute CoVid-19 | Double-blind randomized trial |
| Safa 2020a | Glycyrrhiza glabra root | Caps 760 mg tid x 7 d | Iranian adults with moderate acute CoVid-19 | Open randomized trial |
| Azimi 2020 | Myrtus communis fruit | Decoction 5 g with sugar bid x 5 d | Iranian adults with CoVid-19 pneumonia | Open randomized trial |
| Yousefi 2021 | Punica granatum fruit | Juice 500 ml bid x 14 d | Hospitalized Iranian adults with CoVid-19 | Double-blind randomized trial |
| Safa 2020b | Zingiber officinale rhizome | 1000 mg caps tid x 7 d | Iranian adults with severe CoVid-19 | Double-blind randomized trial |
Other Miscellaneous Single Reports of Uncertain Clinical Significance
Actaea cimicifuga = Actaea foetida = Cimicifuga foetida (bugbane, 升麻 shēng má): murine coronavirus and porcine epidemic diarrhea virus replication inhibited in vitro (Kim, et al. 2008).
Angelica keiskei (ashitaba) chalcones inhibited SARS-CoV proteases in vitro (Park, et al. 2016).
Anthemis hyalina: strongly inhibited murine coronavirus replication in vitro (Ulasli, et al. 2014).
Broussonetia papyrifera (paper mulberry) flavonoids: inhibits SARS-CoV protease in vitro (Park, et al. 2017).
Cannabis sativa (cannabis): cannabigerolic and cannabidiolic acids block SARS-CoV-2 cell entry by blocking S protein in vitro (van Breemen et al. 2022).
Cephalotaxus fortunei (Japanese plum yew) compound homoharringtonine = omacetaxine inhibited SAR-CoV-2 replication in vitro (Choy, et al. 2020).
Citrus sinensis (bitter orange): weakly inhibited murine coronavirus replication in vitro (Ulasli, et al. 2014).
Ecklonia cava (brown algae) phloroglucinols (tannin-like compounds) inhibit SARS-CoV proteases in vitro (Park, et al. 2013).
Euphorbia neriifolia (Indian spurge tree) triterpenoids: inhibited human coronavirus 229E activity in vitro (Chang, et al. 2012).
The flavonoids herbacetin, rhoifolin and pectolinarin all inhibited SARS-CoV protease in vitro (Jo, et al. 2020). Rutin and hesperidin were extremely potent at inhibiting SARS-CoV-2 protease in vitro (Das, et al. 2020).
Isatis tinctoria = I. indigotica (woad): extract and its constituents aloe emodin and hesperetin inhibited SARS-CoV protease in vitro (Lin, et al. 2005).
Lobelia inflata (lobelia) compound emetine inhibited SAR-CoV-2 replication in vitro (Choy, et al. 2020). It was synergistic with remdesivir. Emetine also inhibited SARS-CoV-2 protease in vitro (Das, et al. 2020).
Lonicera japonica (Japanese honeysuckle, 金銀花 jīn yín huā) phenylpropanoids showed good activity against SARS-CoV-2 3C-like protease in vitro (Zhu, et al. 2022).
Melia toosendan (chinaberry): murine coronavirus and porcine epidemic diarrhea virus replication inhibited in vitro (Kim, et al. 2008).
Piper longum (long pepper) alkaloid piperine inhibited SARS-CoV-2 spike protein and ACE2 receptor in vitro (Maurya, et al. 2020). This suggests it could have preventative value against CoVid-19.
Salvia miltorrhiza (red sage) tanshinones inhibits SARS-CoV proteases in vitro (Park, et al. 2012).
Sophora tonkinensis = S. subprostrata (bushy sophora, 山豆根 shān dòu gēn): murine coronavirus and porcine epidemic diarrhea virus replication inhibited in vitro (Kim, et al. 2008).
Withania somnifera (ashwagandha) compound withaferin A inhibited SARS-CoV-2 spike protein and ACE2 receptor in vitro (Maurya, et al. 2020). This suggests it could have preventative value against CoVid-19.
Angelica keiskei (ashitaba) chalcones inhibited SARS-CoV proteases in vitro (Park, et al. 2016).
Anthemis hyalina: strongly inhibited murine coronavirus replication in vitro (Ulasli, et al. 2014).
Broussonetia papyrifera (paper mulberry) flavonoids: inhibits SARS-CoV protease in vitro (Park, et al. 2017).
Cannabis sativa (cannabis): cannabigerolic and cannabidiolic acids block SARS-CoV-2 cell entry by blocking S protein in vitro (van Breemen et al. 2022).
Cephalotaxus fortunei (Japanese plum yew) compound homoharringtonine = omacetaxine inhibited SAR-CoV-2 replication in vitro (Choy, et al. 2020).
Citrus sinensis (bitter orange): weakly inhibited murine coronavirus replication in vitro (Ulasli, et al. 2014).
Ecklonia cava (brown algae) phloroglucinols (tannin-like compounds) inhibit SARS-CoV proteases in vitro (Park, et al. 2013).
Euphorbia neriifolia (Indian spurge tree) triterpenoids: inhibited human coronavirus 229E activity in vitro (Chang, et al. 2012).
The flavonoids herbacetin, rhoifolin and pectolinarin all inhibited SARS-CoV protease in vitro (Jo, et al. 2020). Rutin and hesperidin were extremely potent at inhibiting SARS-CoV-2 protease in vitro (Das, et al. 2020).
Isatis tinctoria = I. indigotica (woad): extract and its constituents aloe emodin and hesperetin inhibited SARS-CoV protease in vitro (Lin, et al. 2005).
Lobelia inflata (lobelia) compound emetine inhibited SAR-CoV-2 replication in vitro (Choy, et al. 2020). It was synergistic with remdesivir. Emetine also inhibited SARS-CoV-2 protease in vitro (Das, et al. 2020).
Lonicera japonica (Japanese honeysuckle, 金銀花 jīn yín huā) phenylpropanoids showed good activity against SARS-CoV-2 3C-like protease in vitro (Zhu, et al. 2022).
Melia toosendan (chinaberry): murine coronavirus and porcine epidemic diarrhea virus replication inhibited in vitro (Kim, et al. 2008).
Piper longum (long pepper) alkaloid piperine inhibited SARS-CoV-2 spike protein and ACE2 receptor in vitro (Maurya, et al. 2020). This suggests it could have preventative value against CoVid-19.
Salvia miltorrhiza (red sage) tanshinones inhibits SARS-CoV proteases in vitro (Park, et al. 2012).
Sophora tonkinensis = S. subprostrata (bushy sophora, 山豆根 shān dòu gēn): murine coronavirus and porcine epidemic diarrhea virus replication inhibited in vitro (Kim, et al. 2008).
Withania somnifera (ashwagandha) compound withaferin A inhibited SARS-CoV-2 spike protein and ACE2 receptor in vitro (Maurya, et al. 2020). This suggests it could have preventative value against CoVid-19.
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