There are a few ways that we can fight the novel coronavirus (SARS-CoV-2). Clinical trials aimed at vaccination have recently begun, and at the earliest, could be available within 6-18 months. Similarly, drugs aimed at inhibiting, blocking, or reducing viral replication, including remdesevir and hydoxychloroquine are entering clinical trials, but large-scale results are also a few months away.
Other alternatives that are rarely discussed are dietary components that can inhibit SARS-CoV-2 replication. Inhibiting replication is important because if the virus continually makes more copies of itself, there will be a systemic viral overload, thereby overwhelming the immune system. Two coronavirus proteins that are important for its replication and binding to cell membranes are its Main protease (Mpro for SARS-CoV-2, 3CLpro for SARS-CoV; X. Liu & Wang, 2020), and its surface Spike glycoprotein (S protein; Song et al. 2018), respectively.
In a recently published (but not peer-reviewed) preprint, Tallei et al. (2020) used a molecular docking approach to predict how SARS-CoV-2’s Mpro and S proteins interact with various drugs and plant-based compounds. A lower molecular docking value is indicative of a potentially better ability to inhibit these proteins. Interestingly, many plant-based metabolites have lower (or equal) molecular docking values when compared with coronavirus-based drugs:
For example, when compared with the drugs nelfinavir, hyrdroxychloroquine sulfate, and chloroquine, hesperidin (found in citrus fruits and peppermint) and epigallocatechin galleate (found in green tea, apple skin, plums, onions, hazelnut) had equivalent or lower molecular docking scores, evidence that suggests a better ability for the plant-based metabolites to inhibit Mpro and the S protein. Based on this data, incorporation of these foods may be an important strategy for boosting endogenous defense against SARS-CoV-2 infection.
Similarly, a molecular docking approach was used to identify potential inhibitors for Mpro in another recent preprint (Khaerunnisa et al. 2020). When compared with the docking energy for Mpro’s native ligand (-8), the coronavirus drugs nelfinavir and lopinavir had lower docking energies, thereby suggesting that they would be good Mpro inhibitors. Interestingly, kaempferol and quercetin had docking energies that were not as low as the drugs, but were as low as or lower than the docking energy for Mpro’s native ligand, thereby suggesting that they might also act as inhibitors of SARS-CoV-2 replication:
Kaempferol and quercetin are found in relatively high amounts in dill, lettuce, onions, spinach and other vegetables (for the full list see https://www.ars.usda.gov/ARSUserFiles/80400525/Data/Flav/Flav_R03.pdf).
It’s important to note that the amount of these foods needed to ingest enough kaempferol, quercetin, or other metabolites that may inhibit SARS-CoV-2 replication or its fusion to cell membranes proteins in vivo is unknown. In addition, with the goal of further boosting endogenous defense, I’d propose including these foods in addition to, but not for the replacement of a vaccine or FDA approved medicines. Note that clinical trials aimed at direct testing for the ability of these plant-based components to inhibit SARS-CoV-2 replication has yet to be performed, but when consumed as a part of a whole-food diet, may be a low risk, high reward strategy for battling SARS-CoV-2 infection.
Khaerunnisa, S., Kurniawan, H., Awaluddin R., Suhartati S., Soetjipto, S. (2020). Potential Inhibitor of COVID-19 Main Protease (Mpro) from Several Medicinal Plant Compounds by Molecular Docking Study. March 13, Preprint. doi: 10.20944/preprints202003.0226.v1
Liu, X., & Wang, X.-J. (2020). Potential inhibitors for 2019-nCoV coronavirus M protease from clinically approved medicines. BioRxiv, 2020.01.29.924100. https://doi.org/10.1101/2020.01.29.924100.
Song, W., Gui, M., Wang, X., & Xiang, Y. (2018). Cryo-EM structure of the SARS coronavirus spike glycoprotein in complex with its host cell receptor ACE2. PLOS Pathogens, 14(8), e1007236. https://doi.org/10.1371/journal.ppat.1007236.
Tallei, T.E., Tumilaar, S.G., Niode, N.J. , Fatimawali, Kepel4, B.J., Idroes, R., Effendi Y. (2020). Potential of Plant Bioactive Compounds as SARS-CoV-2 Main Protease (Mpro) and Spike (S) Glycoprotein Inhibitors: A Molecular Docking Study. April 9, Preprint. doi: 10.20944/preprints202004.0102.v2.
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Very useful information.
Thanks for this, Mike. I like the approach and valuable strategies may come of it, but I think you could put more emphasis on the question of dose and the levels attainable in different tissues. I often see in vitro studies using concentrations orders of magnitude higher than anything achievable in vivo. That said, the potential downside of these dietary interventions is basically zero, save that some dopes might change their behaviour thinking they’re protected.
I’d like to see similar analyses for interference with the viral RNA polymerase and other aspects of the virus’s operation.
Yes, of course, Mike. I used to spend a lot of time converting in vitro and animal-based concentrations into human-equivalent doses, but there’s potentially so much inter-individual variability that it’s still just a guess. As you mentioned, including those foods has basically no downside, and I’m hopeful that there will be studies to test their efficacy in human studies. I also agree about similar analyses for other viral-dependent-processes.
Eat lots of capers.
Ha, I tried, but they taste terrible to me! I’ve added more dill, though.