A Retinol Derivative Inhibits SARS-CoV-2 Infection by Interrupting Spike-Mediated Cellular Entry

Tong et al., mBio, doi:10.1128/mbio.01485-22, Jul 2022

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https://c19early.org/tong.html

Vitamin A for COVID-19

46th treatment shown to reduce risk in June 2023, now with p = 0.0052 from 15 studies.

Lower risk for recovery and cases.

No treatment is 100% effective. Protocols combine treatments.

5,700+ studies for 169 treatments. c19early.org

In Vitro study showing all-trans retinoic acid, a vitamin A derivative, has potent antiviral activity against SARS-CoV-2 in both human cell lines and human organoids of the lower respiratory tract.

11 preclinical studies support the efficacy of vitamin A for COVID-19:

5 In Silico studies1-5

5 In Vitro studies2,6-9

1 In Vivo animal study10

Vitamin A has been identified by the European Food Safety Authority (EFSA) as having sufficient evidence for a causal relationship between intake and optimal immune system function11-13. Vitamin A has potent antiviral activity against SARS-CoV-2 in both human cell lines and human organoids of the lower respiratory tract (active metabolite all-trans retinoic acid, ATRA)8, is predicted to bind critical host and viral proteins for SARS-CoV-2 and may compensate for gene expression changes related to SARS-CoV-22-4, may be beneficial for COVID-19 via antiviral, anti-inflammatory, and immunomodulatory effects according to network pharmacology analysis5, reduces barrier compromise caused by TNF-α in Calu-3 cells7, inhibits mouse coronavirus replication10, may stimulate innate immunity by activating interferon responses in an IRF3-dependent manner (ATRA)10, may reduce excessive inflammation induced by SARS-CoV-22, shows SARS-CoV-2 antiviral activity In Vitro2,6,9, is effective against multiple SARS-CoV-2 variants in Calu-3 cells9, and inhibits the entry and replication of SARS-CoV-2 via binding to ACE2 / 3CLpro / RdRp / helicase / 3′-to-5′ exonuclease2.

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1. Voloudakis et al., A genetically based computational drug repurposing framework for rapid identification of candidate compounds: application to COVID-19, medRxiv, doi:10.1101/2025.01.10.25320348.medrxiv.org, doi.org.

2. Huang et al., All-trans retinoic acid acts as a dual-purpose inhibitor of SARS-CoV-2 infection and inflammation, Computers in Biology and Medicine, doi:10.1016/j.compbiomed.2024.107942.sciencedirect.com, doi.org.

3. Chakraborty et al., In-silico screening and in-vitro assay show the antiviral effect of Indomethacin against SARS-CoV-2, Computers in Biology and Medicine, doi:10.1016/j.compbiomed.2022.105788.sciencedirect.com, doi.org.

4. Pandya et al., Unravelling Vitamin B12 as a potential inhibitor against SARS-CoV-2: A computational approach, Informatics in Medicine Unlocked, doi:10.1016/j.imu.2022.100951.sciencedirect.com, doi.org.

5. Li et al., Revealing the targets and mechanisms of vitamin A in the treatment of COVID-19, Aging, doi:10.18632/aging.103888.aging-us.com, doi.org.

6. Moatasim et al., Potent Antiviral Activity of Vitamin B12 against Severe Acute Respiratory Syndrome Coronavirus 2, Middle East Respiratory Syndrome Coronavirus, and Human Coronavirus 229E, Microorganisms, doi:10.3390/microorganisms11112777.mdpi.com, doi.org.

7. DiGuilio et al., The multiphasic TNF-α-induced compromise of Calu-3 airway epithelial barrier function, Experimental Lung Research, doi:10.1080/01902148.2023.2193637.tandfonline.com, doi.org.

8. Tong et al., A Retinol Derivative Inhibits SARS-CoV-2 Infection by Interrupting Spike-Mediated Cellular Entry, mBio, doi:10.1128/mbio.01485-22.asm.org, doi.org.

9. Morita et al., All-Trans Retinoic Acid Exhibits Antiviral Effect against SARS-CoV-2 by Inhibiting 3CLpro Activity, Viruses, doi:10.3390/v13081669.mdpi.com, doi.org.

10. Franco et al., Retinoic Acid-Mediated Inhibition of Mouse Coronavirus Replication Is Dependent on IRF3 and CaMKK, Viruses, doi:10.3390/v16010140.mdpi.com, doi.org.

11. Galmés et al., Suboptimal Consumption of Relevant Immune System Micronutrients Is Associated with a Worse Impact of COVID-19 in Spanish Populations, Nutrients, doi:10.3390/nu14112254.mdpi.com, doi.org.

12. Galmés (B) et al., Current State of Evidence: Influence of Nutritional and Nutrigenetic Factors on Immunity in the COVID-19 Pandemic Framework, Nutrients, doi:10.3390/nu12092738.mdpi.com, doi.org.

13. EFSA, Scientific Opinion on the substantiation of health claims related to vitamin A and cell differentiation (ID 14), function of the immune system (ID 14), maintenance of skin and mucous membranes (ID 15, 17), maintenance of vision (ID 16), maintenance of bone (ID 13, 17), maintenance of teeth (ID 13, 17), maintenance of hair (ID 17), maintenance of nails (ID 17), metabolism of iron (ID 206), and protection of DNA, proteins and lipids from oxidative damage (ID 209) pursuant to Article 13(1) of Regulation (EC) No 1924/2006, EFSA Journal, doi:10.2903/j.efsa.2009.1221.europa.eu, doi.org.

Tong et al., 13 Jul 2022, China, peer-reviewed, 14 authors. Contact: gongcheng@mail.tsinghua.edu.cn, yxiang@mail.tsinghua.edu.cn, renlizhangszcdc@aliyun.com, lil@sustech.edu.cn.

In Vitro studies are an important part of preclinical research, however results may be very different in vivo.

This Paper Vitamin A All

A Retinol Derivative Inhibits SARS-CoV-2 Infection by Interrupting Spike-Mediated Cellular Entry

Liangqin Tong, Lin Wang, Shumin Liao, Xiaoping Xiao, Jing Qu, Chunli Wu, Yibin Zhu, Wanbo Tai, Yanhong Huang, Penghua Wang, Liang Li, Renli Zhang, Ye Xiang, Gong Cheng

mBio, doi:10.1128/mbio.01485-22

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent of the global pandemic and life-threatening coronavirus disease 2019 . Although vaccines and therapeutic antibodies are available, their efficacy is continuously undermined by rapidly emerging SARS-CoV-2 variants. Here, we found that all-trans retinoic acid (ATRA), a vitamin A (retinol) derivative, showed potent antiviral activity against all SARS-CoV-2 variants in both human cell lines and human organoids of the lower respiratory tract. Mechanistically, ATRA directly binds in a deep hydrophobic pocket of the receptor binding domain (RBD) located on the top of the SARS-CoV-2 spike protein (S) trimer. The bound ATRA mediates strong interactions between the "down" RBDs and locks most of the S trimers in an RBD "all-down" and ACE2-inaccessible inhibitory conformation. In summary, our results reveal the pharmacological biotargets and structural mechanism of ATRA and other retinoids in SARS-CoV-2 infection and suggest that ATRA and its derivatives could be potential hit compounds against a broad spectrum of coronaviruses. IMPORTANCE Retinoids, a group of compounds including vitamin A and its active metabolite all-trans retinoic acid (ATRA), regulate serial physiological activity in multiple organ systems, such as cell growth, differentiation, and apoptosis. The ATRA analogues reported to date include more than 4,000 natural and synthetic molecules that are structurally and/or functionally related to ATRA. Here, we found that ATRA showed potent antiviral activity against all SARS-CoV-2 variants by directly binding in a deep hydrophobic pocket of the receptor binding domain (RBD) located on top of the SARS-CoV-2 spike protein (S) trimer. The bound ATRA mediates strong interactions between the "down" RBDs and locks most of the S trimers in an RBD "all-down" and ACE2-inaccessible inhibitory conformation, suggesting the pharmacological feasibility of using ATRA or its derivatives as a remedy for and prevention of COVID-19 disease.

References

Altmann, Boyton, Beale, Immunity to SARS-CoV-2 variants of concern, Science, doi:10.1126/science.abg7404

Aluisio, Perera, Yam, Garbern, Peters et al., Vitamin A supplementation was associated with reduced mortality in patients with Ebola virus disease during the West African outbreak, J Nutr, doi:10.1093/jn/nxz142

Ao, Lan, He, Liu, Chen et al., SARS-CoV-2 Omicron variant: immune escape and vaccine development, MedComm, doi:10.1002/mco2.126

Baden, Buxman, Weinstein, Yoder, Treatment of ichthyosis with isotretinoin, J Am Acad Dermatol, doi:10.1016/s0190-9622(82)70062-3

Bangaru, Ozorowski, Turner, Antanasijevic, Huang et al., Structural analysis of full-length SARS-CoV-2 spike protein from an advanced vaccine candidate, Science, doi:10.1126/science.abe1502

Bapna, Nair, Tapan, Nair, Kadam et al., All-trans-retinoic acid (ATRA): pediatric acute promyelocytic leukemia, Pediatr Hematol Oncol, doi:10.3109/08880019809028791

Bates, Vitamin A, Lancet, doi:10.1016/s0140-6736(95)91157-x

Bojkova, Klann, Koch, Widera, Krause et al., Proteomics of SARS-CoV-2-infected host cells reveals therapy targets, Nature, doi:10.1038/s41586-020-2332-7

Böcher, Wallasch, Höhler, Galle, All-trans retinoic acid for treatment of chronic hepatitis C, Liver Int, doi:10.1111/j.1478-3231.2007.01666.x

Chen, Yang, Xu, Su, Effect of all-trans-retinoic acid on enterovirus 71 infection in vitro, Br J Nutr, doi:10.1017/S0007114513004133

Clark, Jit, Warren-Gash, Guthrie, Wang et al., Global, regional, and national estimates of the population at increased risk of severe COVID-19 due to underlying health conditions in 2020: a modelling study, Lancet Glob Health, doi:10.1016/S2214-109X(20)30264-3

Coombs, Tavakkoli, Tallman, Acute promyelocytic leukemia: where did we start, where are we now, and the future, Blood Cancer J, doi:10.1038/bcj.2015.25

Degos, All-trans retinoic acid (ATRA) therapeutical effect in acute promyelocytic leukemia, Biomed Pharmacother, doi:10.1016/0753-3322(92)90083-j

Degos, Wang, All trans retinoic acid in acute promyelocytic leukemia, Oncogene, doi:10.1038/sj.onc.1204763

Dou, Huang, Zeng, Zhou, Jiang et al., Alltrans retinoic acid enhances the effect of Fra-1 to inhibit cell proliferation and metabolism in cervical cancer, Biotechnol Lett, doi:10.1007/s10529-020-02847-8

Emsley, Lohkamp, Scott, Cowtan, Features and development of Coot, Acta Crystallogr D Biol Crystallogr, doi:10.1107/S0907444910007493

Geria, Scheinfeld, Talarozole, a selective inhibitor of P450-mediated all-trans retinoic acid for the treatment of psoriasis and acne, Curr Opin Invest Drugs

Goddard, Huang, Ferrin, Visualizing density maps with UCSF Chimera, J Struct Biol, doi:10.1016/j.jsb.2006.06.010

Gui, Song, Zhou, Xu, Chen et al., Cryo-electron microscopy structures of the SARS-CoV spike glycoprotein reveal a prerequisite conformational state for receptor binding, Cell Res, doi:10.1038/cr.2016.152

Hoffmann, Arora, Groß, Seidel, Hörnich et al., SARS-CoV-2 variants B.1.351 and P.1 escape from neutralizing antibodies, Cell, doi:10.1016/j.cell.2021.03.036

Hu, Guo, Zhou, Shi, Characteristics of SARS-CoV-2 and COVID-19, Nat Rev Microbiol, doi:10.1038/s41579-020-00459-7

Hussey, Klein, A randomized, controlled trial of vitamin A in children with severe measles, N Engl J Med, doi:10.1056/NEJM199007193230304

Kawaguchi, Yu, Honda, Hu, Whitelegge et al., A membrane receptor for retinol binding protein mediates cellular uptake of vitamin A, Science, doi:10.1126/science.1136244

Li, Si, Lou, Wang, Guo et al., All-trans-retinoic acid inhibits mink hair follicle growth via inhibiting proliferation and inducing apoptosis of dermal papilla cells through TGF-b2/Smad2/3 pathway, Acta Histochem, doi:10.1016/j.acthis.2020.151603

Li, Zhang, Zhang, Qin, Zhao, All-trans retinoic acid regulates sheep primary myoblast proliferation and differentiation in vitro, Domest Anim Endocrinol, doi:10.1016/j.domaniend.2019.106394

Liang, Qiao, Liu, Tian, Hui et al., Overview of all-trans-retinoic acid (ATRA) and its analogues: structures, activities, and mechanisms in acute promyelocytic leukaemia, Eur J Med Chem, doi:10.1016/j.ejmech.2021.113451

Liebschner, Afonine, Baker, Bunkóczi, Chen et al., Macromolecular structure determination using X-rays, neutrons and electrons: recent developments in Phenix, Acta Crystallogr D Struct Biol, doi:10.1107/S2059798319011471

Onnis, Chiaverini, Hickman, Dreyfus, Fischer et al., Alitretinoin reduces erythema in inherited ichthyosis, Orphanet J Rare Dis, doi:10.1186/s13023-018-0783-9

Pan, Wang, Tu, A topical medication of all-trans retinoic acid reduces sebum excretion rate in patients with forehead acne, Am J Ther, doi:10.1097/MJT.0000000000000390

Pei, Feng, Zhang, Sun, Li et al., Host metabolism dysregulation and cell tropism identification in human airway and alveolar organoids upon SARS-CoV-2 infection, Protein Cell, doi:10.1007/s13238-020-00811-w

Punjani, Rubinstein, Fleet, Brubaker, cryoSPARC: algorithms for rapid unsupervised cryo-EM structure determination, Nat Methods, doi:10.1038/nmeth.4169

Roels, Vitamin A physiology, JAMA, doi:10.1001/jama.1970.03180060075015

Sandell, Sanderson, Moiseyev, Johnson, Mushegian et al., RDH10 is essential for synthesis of embryonic retinoic acid and is required for limb, craniofacial, and organ development, Genes Dev, doi:10.1101/gad.1533407

Scheres, Chen, Prevention of overfitting in cryo-EM structure determination, Nat Methods, doi:10.1038/nmeth.2115

Scheres, RELION: implementation of a Bayesian approach to cryo-EM structure determination, J Struct Biol, doi:10.1016/j.jsb.2012.09.006

Shi, Dong, Rapid global spread of the SARS-CoV-2 Delta (B.1 .617.2) variant: spatiotemporal variation and public health impact, doi:10.15212/ZOONOSES-2021-0005

Song, Gui, Wang, Xiang, Cryo-EM structure of the SARS coronavirus spike glycoprotein in complex with its host cell receptor ACE2, PLoS Pathog, doi:10.1371/journal.ppat.1007236

Sun, Chen, Gu, Yang, Wang et al., A mouse model of SARS-CoV-2 infection and pathogenesis, Cell Host Microbe, doi:10.1016/j.chom.2020.05.020

Suzuki, Kunisawa, Vitamin-mediated immune regulation in the development of inflammatory diseases, Endocr Metab Immune Disord Drug Targets, doi:10.2174/1871530315666150316122128

Tan, Baldwin, Davis, Williamson, Potter et al., Addressing preferred specimen orientation in singleparticle cryo-EM through tilting, Nat Methods, doi:10.1038/nmeth.4347

Tepasse, Vollenberg, Fobker, Kabar, Schmidt et al., Vitamin A plasma levels in COVID-19 patients: a ATRA Inhibits SARS-CoV-2 Spike-Mediated Cellular Entry, mBio Month YYYY

Toelzer, Gupta, Yadav, Borucu, Davidson et al., Free fatty acid binding pocket in the locked structure of SARS-CoV-2 spike protein, Science, doi:10.1126/science.abd3255

Walls, Park, Tortorici, Wall, Mcguire et al., Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein, Cell, doi:10.1016/j.cell.2020.02.058

Wang, Horby, Hayden, Gao, A novel coronavirus outbreak of global health concern, Lancet, doi:10.1016/S0140-6736(20)30185-9

Webb, Villamor, Update: effects of antioxidant and non-antioxidant vitamin supplementation on immune function, Nutr Rev, doi:10.1111/j.1753-4887.2007.tb00298.x

Weisblum, Schmidt, Zhang, Dasilva, Poston et al., Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants, eLife, doi:10.7554/eLife.61312

Who, WHO coronavirus (COVID-19) dashboard

Wrapp, Wang, Corbett, Goldsmith, Hsieh et al., Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation, Science, doi:10.1126/science.abb2507

Wrobel, Benton, Xu, Roustan, Martin et al., SARS-CoV-2 and bat RaTG13 spike glycoprotein structures inform on virus evolution and furin-cleavage effects, Nat Struct Mol Biol, doi:10.1038/s41594-020-0468-7

Xia, Liu, Wang, Xu, Lan et al., Inhibition of SARS-CoV-2 (previously 2019-nCoV) infection by a highly potent pan-coronavirus fusion inhibitor targeting its spike protein that harbors a high capacity to mediate membrane fusion, Cell Res, doi:10.1038/s41422-020-0305-x

Yan, Folic acid-induced animal model of kidney disease, Animal Model Exp Med, doi:10.1002/ame2.12194

Yang, Liu, Zhang, Du, Zhou et al., Characteristic analysis of Omicron-included SARS-CoV-2 variants of concern, MedComm, doi:10.1002/mco2.129

Zhang, Gctf: real-time CTF determination and correction, J Struct Biol, doi:10.1016/j.jsb.2015.11.003

Zhang, Qiao, Yu, Zeng, Shan et al., Bat and pangolin coronavirus spike glycoprotein structures provide insights into SARS-CoV-2 evolution, Nat Commun, doi:10.1038/s41467-021-21767-3

Zheng, Palovcak, Armache, Verba, Cheng et al., MotionCor2: anisotropic correction of beam-induced motion for improved cryo-electron microscopy, Nat Methods, doi:10.1038/nmeth.4193

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