Computational molecular docking and virtual screening revealed promising SARS-CoV-2 drugs

Hosseini et al., Precision Clinical Medicine, doi:10.1093/pcmedi/pbab001

Jan 2021

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In Silico study identifying novel ligands as potential inhibitors for SARS-CoV-2, including antiemetics rolapitant and ondansetron for M^pro; labetalol and levomefolic acid for PLpro; and leucal and antifungal natamycin for RdRp.

14 preclinical studies support the efficacy of vitamin B9 for COVID-19:

9 In Silico studies1-9

4 In Vitro studies2,3,10,11

1 In Vivo animal study11

Vitamin B9 has been identified by the European Food Safety Authority (EFSA) as having sufficient evidence for a causal relationship between intake and optimal immune system function12-14. Vitamin B9 inhibits SARS-CoV-2 In Silico3-11, reduces spike protein binding ability11, binds with the spike protein receptor binding domain for alpha and omicron variants2, inhibits the SARS-CoV-2 nucleocapsid protein3, inhibits 3CLpro and PLpro in enzymatic assays2, significantly reduces infection for alpha and omicron SARS-CoV-2 pseudoviruses2, and inhibits ACE2 expression and SARS-CoV-2 infection in a mouse model11.

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1. Wu et al., Biomarkers Prediction and Immune Landscape in Covid-19 and “Brain Fog”, Elsevier BV, doi:10.2139/ssrn.4897774.ssrn.com, doi.org.

2. Pennisi et al., An Integrated In Silico and In Vitro Approach for the Identification of Natural Products Active against SARS-CoV-2, Biomolecules, doi:10.3390/biom14010043.mdpi.com, doi.org.

3. Chen et al., Folic acid: a potential inhibitor against SARS-CoV-2 nucleocapsid protein, Pharmaceutical Biology, doi:10.1080/13880209.2022.2063341.tandfonline.com, doi.org.

4. Eskandari, V., Repurposing the natural compounds as potential therapeutic agents for COVID-19 based on the molecular docking study of the main protease and the receptor-binding domain of spike protein, Journal of Molecular Modeling, doi:10.1007/s00894-022-05138-3.springer.com, doi.org.

5. 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.

6. Serseg et al., Hispidin and Lepidine E: Two Natural Compounds and Folic Acid as Potential Inhibitors of 2019-novel Coronavirus Main Protease (2019-nCoVMpro), Molecular Docking and SAR Study, Current Computer-Aided Drug Design, doi:10.2174/1573409916666200422075440.eurekaselect.com, doi.org.

7. Hosseini et al., Computational molecular docking and virtual screening revealed promising SARS-CoV-2 drugs, Precision Clinical Medicine, doi:10.1093/pcmedi/pbab001.oup.com, doi.org.

8. Ugurel et al., Evaluation of the potency of FDA-approved drugs on wild type and mutant SARS-CoV-2 helicase (Nsp13), International Journal of Biological Macromolecules, doi:10.1016/j.ijbiomac.2020.09.138.sciencedirect.com, doi.org.

9. Kumar et al., In silico virtual screening-based study of nutraceuticals predicts the therapeutic potentials of folic acid and its derivatives against COVID-19, VirusDisease, doi:10.1007/s13337-020-00643-6.springer.com, doi.org.

10. 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.

11. Zhang et al., Folic acid restricts SARS-CoV-2 invasion by methylating ACE2, Frontiers in Microbiology, doi:10.3389/fmicb.2022.980903.frontiersin.org, doi.org.

12. 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.

13. 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.

14. EFSA, Scientific Opinion on the substantiation of health claims related to folate and blood formation (ID 79), homocysteine metabolism (ID 80), energy-yielding metabolism (ID 90), function of the immune system (ID 91), function of blood vessels (ID 94, 175, 192), cell division (ID 193), and maternal tissue growth during pregnancy (ID 2882) pursuant to Article 13(1) of Regulation (EC) No 1924/2006, EFSA Journal, doi:10.2903/j.efsa.2009.1213.europa.eu, doi.org.

Hosseini et al., 18 Jan 2021, peer-reviewed, 4 authors. Contact: chwang@llu.edu, oxwang@gmail.com.

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

This Paper Vitamin B9 All

Computational molecular docking and virtual screening revealed promising SARS-CoV-2 drugs

Maryam Hosseini, Wanqiu Chen, Daliao Xiao, Charles Wang

Precision Clinical Medicine, doi:10.1093/pcmedi/pbab001

The pandemic of novel coronavirus disease 2019 (COVID-19) has rampaged the world, with more than 58.4 million confirmed cases and over 1.38 million deaths across the world by 23 November 2020. There is an urgent need to identify effective drugs and vaccines to fight against the virus. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) belongs to the family of coronaviruses consisting of four structural and 16 non-structural proteins (NSP). Three non-structural proteins, main protease (Mpro), papain-like protease (PLpro), and RNAdependent RNA polymerase (RdRp), are believed to have a crucial role in replication of the virus. We applied computational ligand-receptor binding modeling and performed comprehensive virtual screening on FDA-approved drugs against these three SARS-CoV-2 proteins using AutoDock Vina, Glide, and rDock. Our computational studies identified six novel ligands as potential inhibitors against SARS-CoV-2, including antiemetics rolapitant and ondansetron for Mpro; labetalol and levomefolic acid for PLpro; and leucal and antifungal natamycin for RdRp. Molecular dynamics simulation confirmed the stability of the ligand-protein complexes. The results of our analysis with some other suggested drugs indicated that chloroquine and hydroxychloroquine had high binding energy (low inhibitory effect) with all three proteins-Mpro, PLpro, and RdRp. In summary, our computational molecular docking approach and virtual screening identified some promising candidate SARS-CoV-2 inhibitors that may be considered for further clinical studies.

Supplementary data Supplementary data are available at PCMEDI online. Conflict of interest statement All authors declared no conflict of interests. In addition, as an Editorial Board Member of Precision Clinical Medicine, the corresponding author Charles Wang was blinded from reviewing and making decision on this manuscript.

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'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2022, 12, 12]], 'date-time': '2022-12-12T02:16:32Z', 'timestamp': 1670811392000}, 'score': 1, 'resource': {'primary': {'URL': 'https://academic.oup.com/pcm/article/4/1/1/6103931'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2021, 1, 18]]}, 'references-count': 73, 'journal-issue': { 'issue': '1', 'published-online': {'date-parts': [[2021, 1, 18]]}, 'published-print': {'date-parts': [[2021, 4, 3]]}}, 'URL': 'http://dx.doi.org/10.1093/pcmedi/pbab001', 'relation': {}, 'ISSN': ['2096-5303', '2516-1571'], 'subject': ['General Medicine'], 'published-other': {'date-parts': [[2021, 3]]}, 'published': {'date-parts': [[2021, 1, 18]]}}

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