Multiple lines of research demonstrate that St Johns wort is a source of several compounds that are effective against the SARS-2 virus. Hypericin, pseudohypericin, and isohypericin have all demonstrated the ability to bind to the virus and interfere with its spread at relatively low doses. This research is relevant both to people who have an acute infection or reinfection, and also to those with Long Covid who might have simmering pockets of viral infection that can keep the immune system over-activated.
“Hypericum perforatum and Its Ingredients Hypericin and Pseudohypericin Demonstrate an Antiviral Activity against SARS-CoV-2.” Pharmaceuticals 2022, 25 April 2022, PMID 35631357, Full Article.
The average person might think of St Johns wort (SJW) as an herb to treat depression (and it works as well as the SSRIs for that), but it has a number of other uses. It has traditionally been used for pinched nerves and other neuropathic pain, and in recent times, as an antiviral. The flowers were traditionally steeped in oil and resulted in a deep red colored medicine that was used in liniments.
Other Research
A paper published in an American Chemical Society paper reveals that St Johns wort works against the SARS2 virus in a number of ways. It describes hypericin as being effective at nanomolar doses when activated by blue light … active at parts per billion. Hypericin in the dark was also active, but less so. (Hypericin is a photo-sensitizer, so people taking it should not get prolonged sun exposure).
“The Interaction of Hypericin with SARS-CoV-2 Reveals a Multimodal Antiviral Activity.” ACS Applied Material Interfaces, 30 Mar 2022, PMID 35302731.
This study found that hypericin binds with high affinity to 2 viral proteins (Mpro and RdRp) and is able to interfere with the virus life cycle by doing so. It also found that hypericin was not toxic to cells at doses that effectively inhibited the virus. This makes hypericin different from other potential therapies (like raw cannabinoids) which target the virus spike protein.
“Identification of Hypericin as a Candidate Repurposed Therapeutic Agent for COVID-19 and Its Potential Anti-SARS-CoV-2 Activity.” Frontiers in Microbiology, 10 Feb 2022, PMID 35222340, Full Article.
This study looked at the ability of hypericin, other dietary molecules, and anti-viral pharmaceuticals to bind to the PL protein of the SARS2 virus and inhibit a process called deubiquitinating. This process is critical to how the virus breaks down cell walls to get in and out. Hypericin and the experimental pharmaceutical GRL-0167 were the most active, with this ranking: GRL-0167, hypericin >> rutin, cyanidin-3-O-glucoside > epigallocatechin gallate, epicatechin gallate, and cefotaxime.
“Identification of Small Molecule Inhibitors of the Deubiquitinating Activity of the SARS-CoV-2 Papain-Like Protease: in silico Molecular Docking Studies and in vitro Enzymatic Activity Assay.” Frontiers in Chemistry, 8 Dec 2020, PMID 33364229, Full Article.
A study was done on the effects of hypericin on a coronavirus that infects pigs (which is related to the SARS2 virus that causes covid-19). It was suggested that hypericin binds to two parts of the virus surface that tend not to mutate very often - suggesting that new variants of the alphacoronavirus will likely still be vulnerable to hypericin.
“Hypericin Inhibit Alpha-Coronavirus Replication by Targeting 3CL Protease.” Viruses, 14 Sep 2021, PMID 34578406, Full Article.
A study in China compared Saquinavir (an anti-viral medicine used for HIV/AIDS) to 2 herbal compounds (hypericin and baicalein) and bromocriptine (a drug used for Parkinson’s disease that is also known to have antiviral properties). The researchers were interested in how the 4 compounds would bind to the NSP14 site on the surface of the SARS2 virus. Saquinavir showed the tightest binding and greatest potential inhibition of the virus by this measure, but hypericin, baicalein and bromocriptine all showed high scores and the study concluded that all four molecules showed promise against SARS2.
“Potential treatment with Chinese and Western medicine targeting NSP14 of SARS-CoV-2.” Journal of Pharmaceutical Analysis, Jun 2021, PMID 32923004, Full Article.
In a study where 1033 medicinal herbal compounds docked with ACE2, TMPRSS2, GRP78, and AT1R receptors, it was concluded that hypericin, berbamine, and hesperidin showed the most activity that could interfere with the SARS2 virus at these 4 sites.
“Predicted therapeutic targets for COVID-19 disease by inhibiting SARS-CoV-2 and its related receptors.” Informatics in Medicine Unlocked, 7 Aug 2020, PMID 32835083, Full Article.
A molecular docking study was carried out to determine how tightly natural compounds bound to a particular portion of the SARS2 main protease, and how this compared to FDA-approved antiviral compounds. The standard pharmaceuticals showed binding scores of -9 to -13 (the larger the negative number, the tighter the binding). The top 10 natural compounds they screened showed binding scores of -10 to -12. Hypericin was third on that list (-11.7). Other compounds that scored high included a green tea compound, rutin, and compounds from birch, ginkgo, sumac spice, and sorbus plants.
“Molecular docking, validation, dynamics simulations, and pharmacokinetic prediction of natural compounds against the SARS-CoV-2 main-protease.” Journal of Biomolecular Structure and Dynamics, Feb 2022, PMID 32897178, Full Article.
A molecular docking study was carried out on 8755 compounds to find molecules that tightly bind to a key part of the SARS2 spike protein. Hypericin came in second only to phthalocyanine blue, a dye that is used by the textile industry and by artists. The researchers suggested that hypericin could be an important part of an antiviral cocktail formulated against SARS2/Covid-19.
“Targeting the SARS-CoV-2 spike glycoprotein prefusion conformation: virtual screening and molecular dynamics simulations applied to the identification of potential fusion inhibitors.” Virus Research, Sep 2020, PMID 32565126, Full Article.
Certainty
It is fairly well established that hypericin and related compounds have anti-viral properties against SARS2 and a variety of other viruses. From a scientific standpoint, it is not clear if SJW is clinically effective in modifying the course of a SARS2/Covid-19 viral infection. If hypericin attached to and blocked only one molecular target, the case would not be very strong. But hypericin has a high affinity to so many different targets involved in Covid, and this points towards a higher likelihood of having real benefits. I would not bet my life on this (and I am vaccinated and boosted and I take other precautions), but I certainly would add SJW as a supplement that might reduce risk and reduce symptoms of infection.
Personal Anecdote: from 2000 to 2002, a family member was in the hospital for several months, they went in and out of comas, and I spent many days in the hospital while the situation was touch and go. I started taking SJW early on to help deal with the emotional stress, and took it regularly for about 2 years. At the time, I was teaching at a university and typically came down with 2 or 3 colds each year (thanks, kids!). But during this time I took SJW, I did not have a single cold. While that is not a scientifically controlled study, it suggests to me that hypericin can indeed provide some defense against respiratory viruses.
Safety
A meta-anlysis of the research on St Johns wort looked at 29 double-blinded studies that included 5489 patients. It concluded that extracts of the herb “…are similarly effective to standard antidepressants but with fewer side effects.” 1
Most short-term side effects tend to be minor, involving things like an upset stomach. SJW can make some people more sensitive to the sun or ultraviolet light.
Hypericin affects neurotransmitters, and there is a potential for more serious short-term interaction when taking any medicine that affects neurotransmitters. A systematic review 2 of the safety found:
“Case reports or case series suggest interactions of St John’s wort with adrenergic vasopressors, anaesthetics, bupropion, buspirone, ciclosporin, eletriptan, loperamide, nefazodone, nevirapine, oral contraceptives, paroxetine, phenprocoumon, prednisone, sertraline, tacrolimus, theophylline, tibolone, tryptophan, venlafaxine and warfarin.”
The systematic review also noted the use of the herb increases the rate that the liver processes and clears certain medicines, and possibly:
“reduces the plasma concentrations (and/or increases the clearance) of alprazolam, amitriptyline, atorvastatin, chlorzoxazone, ciclosporin, debrisoquine, digoxin, erythromycin, fexofenadine, gliclazide, imatinib, indinavir, irinotecan, ivabradine, mephenytoin, methadone, midazolam, nifedipine, omeprazole, oral contraceptives, quazepam, simvastatin, tacrolimus, talinolol, verapamil, voriconazole and warfarin.”
People who are considering taking St Johns wort are advised to further research potential side effects.
Cost
St Johns wort that contains a standardized amount of hypericin is inexpensive - capsules typically cost 5 to 10 cents retail, and taking SJW for a short period of time is less than a typical co-pay for a prescription.
Dosage and Administration
Commercial SJW products often contain 300 mg of extract that is standardized to contain 0.3 hypericin (0.9 mg per tablet or capsule). Common doses are 3 such capsules over the course of a day, or 2.7 mg hypericin per day.
When I take SJW for a respiratory infection, I let it dissolve in my mouth. This creates a higher concentration in the throat tissues for a short period, which might assist in tagging and inactivating the virus particles that are present there. The herb or extract has a less than luxurious taste, but it is tolerable on occasions.
Quality
Fresh, high-quality St Johns wort has a unique aroma; it has a particular medicinal smell that is easy to remember. Capsules containing older, lower-quality dried herb lack that zing. Some extracts might not have that aroma, and products that are enterically sealed might lack it. But when I open a bottle of SJW and smell that smell, I find it assuring.
Bottom Line
We don’t know for certain how effective SJW is for treating respiratory infections in people, but there is a solid rationale for its use. The herb is fairly well studied and millions of people have used it for treating depression and other mood instabilities. The risks of this option are not zero but seem fairly low. People taking other prescription medicines need to do more research on possible interactions. The research suggests that hypericin is more powerful than other dietary anti-viral molecules like rutin and green tea catechins, and it has been shown to interfere with multiple components of the virus. Saint Johns wort (with its hypericin) is in my kitchen cabinet, and I look forward to following the research on this option and writing more about it in the future.
Footnotes
“Review: St John’s wort superior to placebo and similar to antidepressants for major depression but with fewer side effects.” Evidence Based Mental Health, Aug 2009, PMID 19633246.