Vitamin D is a New Promising Inhibitor to the Main Protease (Mpro) of COVID-19 by Molecular Docking

Al-Mazaideh et al., Journal of Pharmaceutical Research International, doi:10.9734/jpri/2021/v33i29B31603

May 2021

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In Silico study showing vitamin D binding with M^pro of SARS-CoV-2. Among the compounds tested, vitamin D had the highest potential interaction in terms of total H-bond, van der Waal, torsional, and desolvation energy. Authors recommend adding vitamin D to COVID-19 treatment protocols.

12 preclinical studies support the efficacy of vitamin D for COVID-19:

6 In Silico studies Al-Mazaideh, Chellasamy, Mansouri, Pandya, Qayyum, Song

5 In Vitro studies DiGuilio, Mok, Pickard, Rybakovsky, Sposito

1 In Vivo animal study Fernandes de Souza

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1. Al-Mazaideh et al., Vitamin D is a New Promising Inhibitor to the Main Protease (Mpro) of COVID-19 by Molecular Docking, Journal of Pharmaceutical Research International, doi:10.9734/jpri/2021/v33i29B31603.journaljpri.com, doi.org.

2. Chellasamy et al., Docking and molecular dynamics studies of human ezrin protein with a modelled SARS-CoV-2 endodomain and their interaction with potential invasion inhibitors, Journal of King Saud University - Science, doi:10.1016/j.jksus.2022.102277.sciencedirect.com, doi.org.

3. 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.

4. Fernandes de Souza et al., Lung Inflammation Induced by Inactivated SARS-CoV-2 in C57BL/6 Female Mice Is Controlled by Intranasal Instillation of Vitamin D, Cells, doi:10.3390/cells12071092.mdpi.com, doi.org.

5. Mansouri et al., The impact of calcitriol and estradiol on the SARS-CoV-2 biological activity: a molecular modeling approach, Scientific Reports, doi:10.1038/s41598-022-04778-y.nature.com, doi.org.

6. Mok et al., Calcitriol, the active form of vitamin D, is a promising candidate for COVID-19 prophylaxis, bioRxiv, doi:10.1101/2020.06.21.162396.biorxiv.org, doi.org.

7. 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.

8. Pickard et al., Discovery of re-purposed drugs that slow SARS-CoV-2 replication in human cells, PLOS Pathogens, doi:10.1371/journal.ppat.1009840.plos.org, doi.org.

9. Qayyum et al., Vitamin D and lumisterol novel metabolites can inhibit SARS-CoV-2 replication machinery enzymes, Endocrinology and Metabolism, doi:10.1152/ajpendo.00174.2021.physiology.org, doi.org.

10. Rybakovsky et al., Calcitriol modifies tight junctions, improves barrier function, and reduces TNF‐α‐induced barrier leak in the human lung‐derived epithelial cell culture model, 16HBE 14o‐, Physiological Reports, doi:10.14814/phy2.15592.wiley.com, doi.org.

11. Song et al., Vitamin D3 and its hydroxyderivatives as promising drugs against COVID-19: a computational study, Journal of Biomolecular Structure and Dynamics, doi:10.1080/07391102.2021.1964601.tandfonline.com, doi.org.

12. Sposito et al., Age differential CD13 and interferon expression in airway epithelia affect SARS-CoV-2 infection - effects of vitamin D, Mucosal Immunology, doi:10.1016/j.mucimm.2023.08.002.nih.gov, doi.org.

Al-Mazaideh et al., 26 May 2021, peer-reviewed, 4 authors.

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

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Vitamin D is a New Promising Inhibitor to the Main Protease (Mpro) of COVID-19 by Molecular Docking

Ghassab M Al-Mazaideh, Mohammed H Shalayel, Farhan K Al-Swailmi, Saleem H Aladaileh

Journal of Pharmaceutical Research International, doi:10.9734/jpri/2021/v33i29b31603

In this study, vitamin D has shown greater efficacy of binding with M pro of COVID-19 compared to the recently recommended drugs. The docking study was simulated to streamline interaction effects of Vitamin D, Remdesivir, Chloroquine, Hydroxychloroquine, Aspirin, and Azithromycin complexes with the active site of M pro . Vitamin D is found to have the highest potential interaction in terms of total H-bond, van der Waal, torsional, and desolvation energy which were the lowest among all the selected drugs. The hydroxyl group of vitamin D and the thiol group of M pro cysteine had played a leading role in increasing Vitamin D binding and stability with the M pro pocket by contribution to the inception of three hydrogen bonds. The study recommend that vitamin D can be added to the COVID-19 treatment protocol, which may have the desired effect on viral replication inhibition and decreases mortality.

CONSENT It's not applicable. ETHICAL APPROVAL It's not applicable. COMPETING INTERESTS Authors have declared that no competing interests exist.

References

Baez-Santos, John, Mesecar, The SARS-coronavirus papain-like protease: Structure, function and inhibition by designed antiviral compounds, Antivir. Res

Bikle, Vitamin D metabolism, mechanism of action and clinical applications, Chem. Biol, doi:10.1016/j.chembiol.2013.12.016

Brooijmans, Kuntz, Molecular recognition and docking algorithms, Annual Rev. Biophys. Biomol. Struct

Chauhan, Kalra, Identification of potent COVID-19 main protease (M PRO ) inhibitors from flavonoids, Res. square. Preprint, doi:10.21203/rs.3.rs-34497/v1

Forli, Huey, Pique, Sanner, Goodsell et al., Computational protein-ligand docking and virtual drug screening with the Auto Dock suite, Nat. Protoc, doi:10.1038/nprot.2016.051

Hansdottir, Monick, Vitamin D effects on lung immunity and respiratory diseases, Vitam. Horm

Jin, Du, Xu, Deng, Liu et al., Structure of M pro from SARS-CoV-2 and discovery of its inhibitors, Nature

Joshi, Joshi, Sharma, Mathpal, Pundir et al., In silico screening of natural compounds against COVID-19 by targeting Mpro and ACE2 using molecular docking, Eur. Rev. Med. Pharmacol. Sci

Jung, Akhmetzhanov, Hayashi, Linton, Yang et al., Real-Time Estimation of the Risk of Death from Novel Coronavirus (COVID-19) Infection: Inference Using Exported Cases, J. Clin. Med

Larriba, De Herreros, Muñoz, Vitamin D and the Epithelial to Mesenchymal Transition, Stem Cells Inter, doi:10.1155/2016/6213872

Lybrand, Ligand-protein docking and rational drug design, Curr. Opin. Struct. Biol

Martineau, Jolliffe, Greenberg, Aloia, Bergman et al., Vitamin D supplementation to prevent acute respiratory infections: individual participant data meta-analysis, Health Technol. Assess, doi:10.3310/hta23020

Motiwale, Yadav, Kumar, Kushwaha, Choudhir et al., Finding potent inhibitors for COVID-19 main protease (M pro ): an in silico approach using SARS-CoV-3CL protease inhibitors for combating CORONA, J. Biomol. Struct. Dyn, doi:10.1080/07391102.2020.1829501

Narkhede, Pise, Cheke, Cheke, Shinde, Recognition of Natural Products as Potential Inhibitors of COVID-19 Main Protease (Mpro): In-Silico Evidences, Nat. Prod. Bioprospect, doi:10.1007/s13659-020-00253-1

Pell, Kuang, Viboud, Chowell, Using phenomenological models for forecasting the 2015 Ebola challenge, Epidemics, doi:10.1016/j.epidem.2016.11.002

Rizvi, Shakil, Haneef, A simple click by click protocol to perform docking: Auto Dock 4.2 made easy for nonbioinformaticians, EXCLI J

Roosa, Lee, Kirpich, Rothenberg, Hyman et al., Real-time forecasts of the COVID-19 epidemic in China from February 5th to February 24 th, Infect. Disease Mod

Shalayel, Al-Mazaideh, Aladaileh, Fk, Mg, Vitamin D is a potential inhibitor of COVID-19: In silico molecular docking to the binding site of SARS-CoV-2

Shalayel, Al-Qahtani, Huneif, Vitamin D or flu vaccine-benefits over adverse effects, Br. Biomed Bull

Wang, Cao, Zhang, Yang, Liu et al., Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro, Cell Res

Xu, Baylink, Chen, Reeves, Xiao et al., The importance of vitamin d metabolism as a potential prophylactic, immunoregulatory and neuroprotective treatment for COVID-19, J. Transl. Med, doi:10.1186/s12967-020-02488-5

Yang, Xie, Xue, Yang, Ma et al., Design of wide-spectrum inhibitors targeting coronavirus main proteases, PLoS Biol

Zhang, Lin, Sun, Curth, Drosten et al., Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved αketoamide inhibitors, Science

Zhang, Shen, Yan, Wang, Cheng, Discovery of anti-SARS-CoV-2 agents from commercially available flavor via docking screening, OSF Preprints

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