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Potential of NO donor furoxan as SARS-CoV-2 main protease (Mpro) inhibitors: in silico analysis.
J Biomol Struct Dyn. 2020 Jul 08 [Online ahead of print]JB

Abstract

The sharp spurt in positive cases of novel coronavirus-19 (SARS-CoV-2) worldwide has created a big threat to human. In view to expedite new drug leads for COVID-19, Main Proteases (Mpro) of novel Coronavirus (SARS-CoV-2) has emerged as a crucial target for this virus. Nitric oxide (NO) inhibits the replication cycle of SARS-CoV. Inhalation of nitric oxide is used in the treatment of severe acute respiratory syndrome. Herein, we evaluated the phenyl furoxan, a well-known exogenous NO donor to identify the possible potent inhibitors through in silico studies such as molecular docking as per target analysis for candidates bound to substrate binding pocket of SARS-COV-2 Mpro. Molecular dynamics (MD) simulations of most stable docked complexes (Mpro-22 and Mpro-26) helped to confirm the notable conformational stability of these docked complexes under dynamic state. Furthermore, Molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) calculations revealed energetic contributions of key residues of Mpro in binding with potent furoxan derivatives 22, 26. In the present study to validate the molecular docking, MD simulation and MM-PBSA results, crystal structure of Mpro bound to experimentally known inhibitor X77 was used as control and the obtained results are presented herein. We envisaged that spiro-isoquinolino-piperidine-furoxan moieties can be used as effective ligand for SARS-CoV-2 Mpro inhibition due to the presence of key isoquinolino-piperidine skeleton with additional NO effect. Communicated by Ramaswamy H. Sarma.

Authors+Show Affiliations

Research center for Advanced Materials Science, King Khalid University, Abha, Saudi Arabia. Department of Chemistry, King Khalid University, Abha, Saudi Arabia.Research center for Advanced Materials Science, King Khalid University, Abha, Saudi Arabia. Department of Chemistry, King Khalid University, Abha, Saudi Arabia.Department of Pharmaceutical Chemistry, Bharati Vidyapeeth College of Pharmacy, Kolhapur, Maharashtra, India.Department of Pharmaceutical Chemistry, Bharati Vidyapeeth College of Pharmacy, Kolhapur, Maharashtra, India.Department of Pharmaceutical Chemistry, Bharati Vidyapeeth College of Pharmacy, Kolhapur, Maharashtra, India.Department of Pharmaceutical Chemistry, Bharati Vidyapeeth College of Pharmacy, Kolhapur, Maharashtra, India.School of Chemical Sciences, SRTM University, Nanded, Maharashtra, India.School of Chemical Sciences, SRTM University, Nanded, Maharashtra, India.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32643550

Citation

Al-Sehemi, Abdullah G., et al. "Potential of NO Donor Furoxan as SARS-CoV-2 Main Protease (Mpro) Inhibitors: in Silico Analysis." Journal of Biomolecular Structure & Dynamics, 2020, pp. 1-15.
Al-Sehemi AG, Pannipara M, Parulekar RS, et al. Potential of NO donor furoxan as SARS-CoV-2 main protease (Mpro) inhibitors: in silico analysis. J Biomol Struct Dyn. 2020.
Al-Sehemi, A. G., Pannipara, M., Parulekar, R. S., Patil, O., Choudhari, P. B., Bhatia, M. S., Zubaidha, P. K., & Tamboli, Y. (2020). Potential of NO donor furoxan as SARS-CoV-2 main protease (Mpro) inhibitors: in silico analysis. Journal of Biomolecular Structure & Dynamics, 1-15. https://doi.org/10.1080/07391102.2020.1790038
Al-Sehemi AG, et al. Potential of NO Donor Furoxan as SARS-CoV-2 Main Protease (Mpro) Inhibitors: in Silico Analysis. J Biomol Struct Dyn. 2020 Jul 8;1-15. PubMed PMID: 32643550.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Potential of NO donor furoxan as SARS-CoV-2 main protease (Mpro) inhibitors: in silico analysis. AU - Al-Sehemi,Abdullah G, AU - Pannipara,Mehboobali, AU - Parulekar,Rishikesh S, AU - Patil,Omkar, AU - Choudhari,Prafulla B, AU - Bhatia,M S, AU - Zubaidha,P K, AU - Tamboli,Yasinalli, Y1 - 2020/07/08/ PY - 2020/7/10/entrez PY - 2020/7/10/pubmed PY - 2020/7/10/medline KW - COVID-19 KW - SARS-CoV-2 Mpro inhibition KW - furoxan KW - in silico analysis KW - nitric oxide SP - 1 EP - 15 JF - Journal of biomolecular structure & dynamics JO - J. Biomol. Struct. Dyn. N2 - The sharp spurt in positive cases of novel coronavirus-19 (SARS-CoV-2) worldwide has created a big threat to human. In view to expedite new drug leads for COVID-19, Main Proteases (Mpro) of novel Coronavirus (SARS-CoV-2) has emerged as a crucial target for this virus. Nitric oxide (NO) inhibits the replication cycle of SARS-CoV. Inhalation of nitric oxide is used in the treatment of severe acute respiratory syndrome. Herein, we evaluated the phenyl furoxan, a well-known exogenous NO donor to identify the possible potent inhibitors through in silico studies such as molecular docking as per target analysis for candidates bound to substrate binding pocket of SARS-COV-2 Mpro. Molecular dynamics (MD) simulations of most stable docked complexes (Mpro-22 and Mpro-26) helped to confirm the notable conformational stability of these docked complexes under dynamic state. Furthermore, Molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) calculations revealed energetic contributions of key residues of Mpro in binding with potent furoxan derivatives 22, 26. In the present study to validate the molecular docking, MD simulation and MM-PBSA results, crystal structure of Mpro bound to experimentally known inhibitor X77 was used as control and the obtained results are presented herein. We envisaged that spiro-isoquinolino-piperidine-furoxan moieties can be used as effective ligand for SARS-CoV-2 Mpro inhibition due to the presence of key isoquinolino-piperidine skeleton with additional NO effect. Communicated by Ramaswamy H. Sarma. SN - 1538-0254 UR - https://www.unboundmedicine.com/medline/citation/32643550/Potential_of_NO_donor_furoxan_as_SARS_CoV_2_main_protease__Mpro__inhibitors:_in_silico_analysis_ L2 - http://www.tandfonline.com/doi/full/10.1080/07391102.2020.1790038 DB - PRIME DP - Unbound Medicine ER -
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