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Withanone and caffeic acid phenethyl ester are predicted to interact with main protease (Mpro) of SARS-CoV-2 and inhibit its activity.
J Biomol Struct Dyn. 2020 Jun 01 [Online ahead of print]JB

Abstract

The recent novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2/2019-nCoV) has caused a large number of deaths around the globe. There is an urgent need to understand this new virus and develop prophylactic and therapeutic drugs. Since drug development is an expensive, intense and time-consuming path, timely repurposing of the existing drugs is often explored wherein the research avenues including genomics, bioinformatics, molecular modeling approaches offer valuable strengths. Here, we have examined the binding potential of Withaferin-A (Wi-A), Withanone (Wi-N) (active withanolides of Ashwagandha) and Caffeic Acid Phenethyl Ester (CAPE, bioactive ingredient of propolis) to a highly conserved protein, Mpro of SARS-CoV-2. We found that Wi-N and CAPE, but not Wi-A, bind to the substrate-binding pocket of SARS-CoV-2 Mpro with efficacy and binding energies equivalent to an already claimed N3 protease inhibitor. Similar to N3 inhibitor, Wi-N and CAPE were interacting with the highly conserved residues of the proteases of coronaviruses. The binding stability of these molecules was further analyzed using molecular dynamics simulations. The binding free energies calculated using MM/GBSA for N3 inhibitor, CAPE and Wi-N were also comparable. Data presented here predicted that these natural compounds may possess the potential to inhibit the functional activity of SARS-CoV-2 protease (an essential protein for virus survival), and hence (i) may connect to save time and cost required for designing/development, and initial screening for anti-COVID drugs, (ii) may offer some therapeutic value for the management of novel fatal coronavirus disease, (iii) warrants prioritized further validation in the laboratory and clinical tests.Communicated by Ramaswamy H. Sarma.

Authors+Show Affiliations

DAILAB, Department of Biochemical Engineering & Biotechnology, Indian Institute of Technology (IIT) Delhi, New Delhi, India.AIST-INDIA DAILAB, DBT-AIST International Center for Translational & Environmental Research (DAICENTER), National Institute of Advanced Industrial Science & Technology (AIST), Tsukuba, Japan.AIST-INDIA DAILAB, DBT-AIST International Center for Translational & Environmental Research (DAICENTER), National Institute of Advanced Industrial Science & Technology (AIST), Tsukuba, Japan.AIST-INDIA DAILAB, DBT-AIST International Center for Translational & Environmental Research (DAICENTER), National Institute of Advanced Industrial Science & Technology (AIST), Tsukuba, Japan.DAILAB, Department of Biochemical Engineering & Biotechnology, Indian Institute of Technology (IIT) Delhi, New Delhi, India.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32431217

Citation

Kumar, Vipul, et al. "Withanone and Caffeic Acid Phenethyl Ester Are Predicted to Interact With Main Protease (Mpro) of SARS-CoV-2 and Inhibit Its Activity." Journal of Biomolecular Structure & Dynamics, 2020, pp. 1-13.
Kumar V, Dhanjal JK, Kaul SC, et al. Withanone and caffeic acid phenethyl ester are predicted to interact with main protease (Mpro) of SARS-CoV-2 and inhibit its activity. J Biomol Struct Dyn. 2020.
Kumar, V., Dhanjal, J. K., Kaul, S. C., Wadhwa, R., & Sundar, D. (2020). Withanone and caffeic acid phenethyl ester are predicted to interact with main protease (Mpro) of SARS-CoV-2 and inhibit its activity. Journal of Biomolecular Structure & Dynamics, 1-13. https://doi.org/10.1080/07391102.2020.1772108
Kumar V, et al. Withanone and Caffeic Acid Phenethyl Ester Are Predicted to Interact With Main Protease (Mpro) of SARS-CoV-2 and Inhibit Its Activity. J Biomol Struct Dyn. 2020 Jun 1;1-13. PubMed PMID: 32431217.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Withanone and caffeic acid phenethyl ester are predicted to interact with main protease (Mpro) of SARS-CoV-2 and inhibit its activity. AU - Kumar,Vipul, AU - Dhanjal,Jaspreet Kaur, AU - Kaul,Sunil C, AU - Wadhwa,Renu, AU - Sundar,Durai, Y1 - 2020/06/01/ PY - 2020/5/21/pubmed PY - 2020/5/21/medline PY - 2020/5/21/entrez KW - Ashwagandha KW - SARS-CoV-2 coronavirus KW - Withaferin-A KW - Withanone KW - binding KW - caffeic acid phenethyl ester KW - honeybee propolis KW - main protease (Mpro) KW - molecular docking SP - 1 EP - 13 JF - Journal of biomolecular structure & dynamics JO - J. Biomol. Struct. Dyn. N2 - The recent novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2/2019-nCoV) has caused a large number of deaths around the globe. There is an urgent need to understand this new virus and develop prophylactic and therapeutic drugs. Since drug development is an expensive, intense and time-consuming path, timely repurposing of the existing drugs is often explored wherein the research avenues including genomics, bioinformatics, molecular modeling approaches offer valuable strengths. Here, we have examined the binding potential of Withaferin-A (Wi-A), Withanone (Wi-N) (active withanolides of Ashwagandha) and Caffeic Acid Phenethyl Ester (CAPE, bioactive ingredient of propolis) to a highly conserved protein, Mpro of SARS-CoV-2. We found that Wi-N and CAPE, but not Wi-A, bind to the substrate-binding pocket of SARS-CoV-2 Mpro with efficacy and binding energies equivalent to an already claimed N3 protease inhibitor. Similar to N3 inhibitor, Wi-N and CAPE were interacting with the highly conserved residues of the proteases of coronaviruses. The binding stability of these molecules was further analyzed using molecular dynamics simulations. The binding free energies calculated using MM/GBSA for N3 inhibitor, CAPE and Wi-N were also comparable. Data presented here predicted that these natural compounds may possess the potential to inhibit the functional activity of SARS-CoV-2 protease (an essential protein for virus survival), and hence (i) may connect to save time and cost required for designing/development, and initial screening for anti-COVID drugs, (ii) may offer some therapeutic value for the management of novel fatal coronavirus disease, (iii) warrants prioritized further validation in the laboratory and clinical tests.Communicated by Ramaswamy H. Sarma. SN - 1538-0254 UR - https://www.unboundmedicine.com/medline/citation/32431217/Withanone_and_caffeic_acid_phenethyl_ester_are_predicted_to_interact_with_main_protease__Mpro__of_SARS_CoV_2_and_inhibit_its_activity_ L2 - http://www.tandfonline.com/doi/full/10.1080/07391102.2020.1772108 DB - PRIME DP - Unbound Medicine ER -
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