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Evaluation of green tea polyphenols as novel corona virus (SARS CoV-2) main protease (Mpro) inhibitors - an in silico docking and molecular dynamics simulation study.
J Biomol Struct Dyn. 2020 Jun 22 [Online ahead of print]JB

Abstract

Coronavirus disease 2019 (COVID-19) is a viral respiratory disease which caused global health emergency and announced as pandemic disease by World Health Organization. Lack of specific drug molecules or treatment strategy against this disease makes it more devastating. Thus, there is an urgent need of effective drug molecules to fight against COVID-19. The main protease (Mpro) of SARS CoV-2, a key component of this viral replication, is considered as a prime target for anti-COVID-19 drug development. In order to find potent Mpro inhibitors, we have selected eight polyphenols from green tea, as these are already known to exert antiviral activity against many RNA viruses. We have elucidated the binding affinities and binding modes between these polyphenols including a well-known Mpro inhibitor N3 (having binding affinity -7.0 kcal/mol) and Mpro using molecular docking studies. All eight polyphenols exhibit good binding affinity toward Mpro (-7.1 to -9.0 kcal/mol). However, only three polyphenols (epigallocatechin gallate, epicatechingallate and gallocatechin-3-gallate) interact strongly with one or both catalytic residues (His41 and Cys145) of Mpro. Molecular dynamics simulations (100 ns) on these three Mpro-polyphenol systems further reveal that these complexes are highly stable, experience less conformational fluctuations and share similar degree of compactness. Estimation of total number of intermolecular H-bond and MM-GBSA analysis affirm the stability of these three Mpro-polyphenol complexes. Pharmacokinetic analysis additionally suggested that these polyphenols possess favorable drug-likeness characteristics. Altogether, our study shows that these three polyphenols can be used as potential inhibitors against SARS CoV-2 Mpro and are promising drug candidates for COVID-19 treatment.Communicated by Ramaswamy H. Sarma.

Authors+Show Affiliations

School of Basic Sciences, Indian Institute of Technology Bhubaneswar, Bhubaneswar, India.School of Basic Sciences, Indian Institute of Technology Bhubaneswar, Bhubaneswar, India.School of Basic Sciences, Indian Institute of Technology Bhubaneswar, Bhubaneswar, India.School of Basic Sciences, Indian Institute of Technology Bhubaneswar, Bhubaneswar, India.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32568613

Citation

Ghosh, Rajesh, et al. "Evaluation of Green Tea Polyphenols as Novel Corona Virus (SARS CoV-2) Main Protease (Mpro) Inhibitors - an in Silico Docking and Molecular Dynamics Simulation Study." Journal of Biomolecular Structure & Dynamics, 2020, pp. 1-13.
Ghosh R, Chakraborty A, Biswas A, et al. Evaluation of green tea polyphenols as novel corona virus (SARS CoV-2) main protease (Mpro) inhibitors - an in silico docking and molecular dynamics simulation study. J Biomol Struct Dyn. 2020.
Ghosh, R., Chakraborty, A., Biswas, A., & Chowdhuri, S. (2020). Evaluation of green tea polyphenols as novel corona virus (SARS CoV-2) main protease (Mpro) inhibitors - an in silico docking and molecular dynamics simulation study. Journal of Biomolecular Structure & Dynamics, 1-13. https://doi.org/10.1080/07391102.2020.1779818
Ghosh R, et al. Evaluation of Green Tea Polyphenols as Novel Corona Virus (SARS CoV-2) Main Protease (Mpro) Inhibitors - an in Silico Docking and Molecular Dynamics Simulation Study. J Biomol Struct Dyn. 2020 Jun 22;1-13. PubMed PMID: 32568613.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Evaluation of green tea polyphenols as novel corona virus (SARS CoV-2) main protease (Mpro) inhibitors - an in silico docking and molecular dynamics simulation study. AU - Ghosh,Rajesh, AU - Chakraborty,Ayon, AU - Biswas,Ashis, AU - Chowdhuri,Snehasis, Y1 - 2020/06/22/ PY - 2020/6/23/entrez PY - 2020/6/23/pubmed PY - 2020/6/23/medline KW - COVID-19 KW - SARS CoV-2 main protease KW - docking KW - green tea polyphenols/catechins KW - molecular dynamics simulation SP - 1 EP - 13 JF - Journal of biomolecular structure & dynamics JO - J. Biomol. Struct. Dyn. N2 - Coronavirus disease 2019 (COVID-19) is a viral respiratory disease which caused global health emergency and announced as pandemic disease by World Health Organization. Lack of specific drug molecules or treatment strategy against this disease makes it more devastating. Thus, there is an urgent need of effective drug molecules to fight against COVID-19. The main protease (Mpro) of SARS CoV-2, a key component of this viral replication, is considered as a prime target for anti-COVID-19 drug development. In order to find potent Mpro inhibitors, we have selected eight polyphenols from green tea, as these are already known to exert antiviral activity against many RNA viruses. We have elucidated the binding affinities and binding modes between these polyphenols including a well-known Mpro inhibitor N3 (having binding affinity -7.0 kcal/mol) and Mpro using molecular docking studies. All eight polyphenols exhibit good binding affinity toward Mpro (-7.1 to -9.0 kcal/mol). However, only three polyphenols (epigallocatechin gallate, epicatechingallate and gallocatechin-3-gallate) interact strongly with one or both catalytic residues (His41 and Cys145) of Mpro. Molecular dynamics simulations (100 ns) on these three Mpro-polyphenol systems further reveal that these complexes are highly stable, experience less conformational fluctuations and share similar degree of compactness. Estimation of total number of intermolecular H-bond and MM-GBSA analysis affirm the stability of these three Mpro-polyphenol complexes. Pharmacokinetic analysis additionally suggested that these polyphenols possess favorable drug-likeness characteristics. Altogether, our study shows that these three polyphenols can be used as potential inhibitors against SARS CoV-2 Mpro and are promising drug candidates for COVID-19 treatment.Communicated by Ramaswamy H. Sarma. SN - 1538-0254 UR - https://www.unboundmedicine.com/medline/citation/32568613/Evaluation_of_green_tea_polyphenols_as_novel_corona_virus__SARS_CoV_2__main_protease__Mpro__inhibitors___an_in_silico_docking_and_molecular_dynamics_simulation_study_ L2 - http://www.tandfonline.com/doi/full/10.1080/07391102.2020.1779818 DB - PRIME DP - Unbound Medicine ER -
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