The incidence of fungi bloodstream infections increases during aging-is that a potential explanation for the presence of fungi in the brains of Alzheimer’s disease patients? Rapamycin is a known antifungal-is it effective against fungi that are found in the blood and brain?
CD8+ T cells are a subset of lymphocytes that play a major role in antiviral defense (Kulinski et al. 2013). However, recently published evidence shows reduced levels of circulating CD8+ T cells in people infected with SARS-CoV-2 (Zheng et al. 2020, Wang et al. 2020; HC= healthy controls, NCP = patients with COVID-19 related pneumonia):
Immune enhancing treatments, including thymalfasin and immunoglobulin are being provided to SARS-COV-2 infected subjects with some success. For example, 37/55 (67%) subjects saw improvements for circulating CD8+ levels in Wang et al. 2020, but additionally, 18/55 subjects did not experience increased CD8+ counts:
Accordingly, levels of CD8+ T cells were identified as an independent predictor for COVID-19 severity and treatment efficacy (Wang et al. 2020). When considering that CD8+ cells were not increased in all subjects in Wang et al., are there are other strategies that may be helpful? Interestingly, increased levels of CD8+ cells are found in the lungs of mice infected with the influenza A virus in response to a high soluble-fiber diet, when compared with control-fed mice (Trompette et al. 2018):
As a result, lung viral load is more than 10-times reduced 8-days after infection in high soluble fiber-fed mice:
Moreover, average survival in mice infected with influenza A is significantly better when fed the high soluble-fiber diet, when compared with control fed-mice:
Is it possible that a high soluble fiber diet can increase CD8+ cells in people infected with SARS-CoV-2, thereby enhancing their recovery and survival? No studies have tested this hypothesis (yet). While conventional medical treatment is obviously helpful, based on the findings of Trompette et al. (2018), further optimization of immune defense against viral infections may occur when including soluble fiber-rich foods.
References
Kulinski JM, Tarakanova VL, Verbsky J. Regulation of antiviral CD8 T-cell responses. Crit Rev Immunol. 2013;33(6):477-88. Review.
Trompette A, Gollwitzer ES, Pattaroni C, Lopez-Mejia IC, Riva E, Pernot J, Ubags N, Fajas L, Nicod LP, Marsland BJ. Dietary Fiber Confers Protection against Flu by Shaping Ly6c– Patrolling Monocyte Hematopoiesis and CD8+ T Cell Metabolism. Immunity. 2018 May 15;48(5):992-1005.e8. doi: 10.1016/j.immuni.2018.04.022.
Wang F, Nie J, Wang H, Zhao Q, Xiong Y, Deng L, Song S, Ma Z, Mo P, Zhang Y. Characteristics of peripheral lymphocyte subset alteration in COVID-19 pneumonia. J Infect Dis. 2020 Mar 30. pii: jiaa150. doi: 10.1093/infdis/jiaa150.
Zheng M, Gao Y, Wang G, Song G, Liu S, Sun D, Xu Y, Tian Z. Functional exhaustion of antiviral lymphocytes in COVID-19 patients. Cell Mol Immunol. 2020 Mar 19. doi: 10.1038/s41423-020-0402-2.
Coronavirus isn’t the only virus that negatively affects human health.
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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.
References
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.
Coronavirus isn’t the only virus that negatively affects human health. For more info,
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Michael Lustgarten 