Virtual screening of anti-HIV1 compounds against SARS-CoV-2: machine learning modeling, chemoinformatics and molecular dynamics simulation based analysis

Abstract COVID-19 caused by the SARS-CoV-2 is a current global challenge and urgent discovery of potential drugs to combat this pandemic is a need of the hour. 3-chymotrypsin-like cysteine protease (3CLpro) enzyme is the vital molecular target against the SARS-CoV-2. Therefore, in the present study,...

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Autores principales:	Mahesha Nand, Priyanka Maiti, Tushar Joshi, Subhash Chandra, Veena Pande, Jagdish Chandra Kuniyal, Muthannan Andavar Ramakrishnan
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/034315f9c3c14c5e806f47e175e55e91
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spelling	oai:doaj.org-article:034315f9c3c14c5e806f47e175e55e912021-12-02T11:40:49ZVirtual screening of anti-HIV1 compounds against SARS-CoV-2: machine learning modeling, chemoinformatics and molecular dynamics simulation based analysis10.1038/s41598-020-77524-x2045-2322https://doaj.org/article/034315f9c3c14c5e806f47e175e55e912020-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-77524-xhttps://doaj.org/toc/2045-2322Abstract COVID-19 caused by the SARS-CoV-2 is a current global challenge and urgent discovery of potential drugs to combat this pandemic is a need of the hour. 3-chymotrypsin-like cysteine protease (3CLpro) enzyme is the vital molecular target against the SARS-CoV-2. Therefore, in the present study, 1528 anti-HIV1compounds were screened by sequence alignment between 3CLpro of SARS-CoV-2 and avian infectious bronchitis virus (avian coronavirus) followed by machine learning predictive model, drug-likeness screening and molecular docking, which resulted in 41 screened compounds. These 41 compounds were re-screened by deep learning model constructed considering the IC50 values of known inhibitors which resulted in 22 hit compounds. Further, screening was done by structural activity relationship mapping which resulted in two structural clefts. Thereafter, functional group analysis was also done, where cluster 2 showed the presence of several essential functional groups having pharmacological importance. In the final stage, Cluster 2 compounds were re-docked with four different PDB structures of 3CLpro, and their depth interaction profile was analyzed followed by molecular dynamics simulation at 100 ns. Conclusively, 2 out of 1528 compounds were screened as potential hits against 3CLpro which could be further treated as an excellent drug against SARS-CoV-2.Mahesha NandPriyanka MaitiTushar JoshiSubhash ChandraVeena PandeJagdish Chandra KuniyalMuthannan Andavar RamakrishnanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-12 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mahesha Nand Priyanka Maiti Tushar Joshi Subhash Chandra Veena Pande Jagdish Chandra Kuniyal Muthannan Andavar Ramakrishnan Virtual screening of anti-HIV1 compounds against SARS-CoV-2: machine learning modeling, chemoinformatics and molecular dynamics simulation based analysis
description	Abstract COVID-19 caused by the SARS-CoV-2 is a current global challenge and urgent discovery of potential drugs to combat this pandemic is a need of the hour. 3-chymotrypsin-like cysteine protease (3CLpro) enzyme is the vital molecular target against the SARS-CoV-2. Therefore, in the present study, 1528 anti-HIV1compounds were screened by sequence alignment between 3CLpro of SARS-CoV-2 and avian infectious bronchitis virus (avian coronavirus) followed by machine learning predictive model, drug-likeness screening and molecular docking, which resulted in 41 screened compounds. These 41 compounds were re-screened by deep learning model constructed considering the IC50 values of known inhibitors which resulted in 22 hit compounds. Further, screening was done by structural activity relationship mapping which resulted in two structural clefts. Thereafter, functional group analysis was also done, where cluster 2 showed the presence of several essential functional groups having pharmacological importance. In the final stage, Cluster 2 compounds were re-docked with four different PDB structures of 3CLpro, and their depth interaction profile was analyzed followed by molecular dynamics simulation at 100 ns. Conclusively, 2 out of 1528 compounds were screened as potential hits against 3CLpro which could be further treated as an excellent drug against SARS-CoV-2.
format	article
author	Mahesha Nand Priyanka Maiti Tushar Joshi Subhash Chandra Veena Pande Jagdish Chandra Kuniyal Muthannan Andavar Ramakrishnan
author_facet	Mahesha Nand Priyanka Maiti Tushar Joshi Subhash Chandra Veena Pande Jagdish Chandra Kuniyal Muthannan Andavar Ramakrishnan
author_sort	Mahesha Nand
title	Virtual screening of anti-HIV1 compounds against SARS-CoV-2: machine learning modeling, chemoinformatics and molecular dynamics simulation based analysis
title_short	Virtual screening of anti-HIV1 compounds against SARS-CoV-2: machine learning modeling, chemoinformatics and molecular dynamics simulation based analysis
title_full	Virtual screening of anti-HIV1 compounds against SARS-CoV-2: machine learning modeling, chemoinformatics and molecular dynamics simulation based analysis
title_fullStr	Virtual screening of anti-HIV1 compounds against SARS-CoV-2: machine learning modeling, chemoinformatics and molecular dynamics simulation based analysis
title_full_unstemmed	Virtual screening of anti-HIV1 compounds against SARS-CoV-2: machine learning modeling, chemoinformatics and molecular dynamics simulation based analysis
title_sort	virtual screening of anti-hiv1 compounds against sars-cov-2: machine learning modeling, chemoinformatics and molecular dynamics simulation based analysis
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/034315f9c3c14c5e806f47e175e55e91
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Virtual screening of anti-HIV1 compounds against SARS-CoV-2: machine learning modeling, chemoinformatics and molecular dynamics simulation based analysis

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