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Phylogenetic Analysis and Structural Perspectives of RNA-Dependent RNA-Polymerase Inhibition from SARs-CoV-2 with Natural Products

ABSTRACT: Most recently, an outbreak of severe pneumonia caused by the infection of SARS-CoV-2, a novel coronavirus first identified in Wuhan, China, imposes serious threats to public health. Upon infecting host cells, coronaviruses assemble a multi-subunit RNA-synthesis complex of viral non-structu...

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Autores principales: Khan, Abbas, Khan, Mazhar, Saleem, Shoaib, Babar, Zainib, Ali, Arif, Khan, Abdul Aziz, Sardar, Zain, Hamayun, Fahad, Ali, Syed Shujait, Wei, Dong-Qing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7332347/
https://www.ncbi.nlm.nih.gov/pubmed/32617855
http://dx.doi.org/10.1007/s12539-020-00381-9
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author Khan, Abbas
Khan, Mazhar
Saleem, Shoaib
Babar, Zainib
Ali, Arif
Khan, Abdul Aziz
Sardar, Zain
Hamayun, Fahad
Ali, Syed Shujait
Wei, Dong-Qing
author_facet Khan, Abbas
Khan, Mazhar
Saleem, Shoaib
Babar, Zainib
Ali, Arif
Khan, Abdul Aziz
Sardar, Zain
Hamayun, Fahad
Ali, Syed Shujait
Wei, Dong-Qing
author_sort Khan, Abbas
collection PubMed
description ABSTRACT: Most recently, an outbreak of severe pneumonia caused by the infection of SARS-CoV-2, a novel coronavirus first identified in Wuhan, China, imposes serious threats to public health. Upon infecting host cells, coronaviruses assemble a multi-subunit RNA-synthesis complex of viral non-structural proteins (nsp) responsible for the replication and transcription of the viral genome. Therefore, the role and inhibition of nsp12 are indispensable. A cryo-EM structure of RdRp from SARs-CoV-2 was used to identify novel drugs from Northern South African medicinal compounds database (NANPDB) by using computational virtual screening and molecular docking approaches. Considering Remdesivir as the control, 42 compounds were shortlisted to have docking score better than Remdesivir. The top 5 hits were validated by using molecular dynamics simulation approach and free energy calculations possess strong inhibitory properties than the Remdesivir. Thus, this study paved a way for designing novel drugs by decoding the architecture of an important enzyme and its inhibition with compounds from natural resources. This disclosing of necessary knowledge regarding the screening and the identification of top hits could help to design effective therapeutic candidates against the coronaviruses and design robust preventive measurements. GRAPHIC ABSTRACT: [Image: see text]
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spelling pubmed-73323472020-07-06 Phylogenetic Analysis and Structural Perspectives of RNA-Dependent RNA-Polymerase Inhibition from SARs-CoV-2 with Natural Products Khan, Abbas Khan, Mazhar Saleem, Shoaib Babar, Zainib Ali, Arif Khan, Abdul Aziz Sardar, Zain Hamayun, Fahad Ali, Syed Shujait Wei, Dong-Qing Interdiscip Sci Original Research Article ABSTRACT: Most recently, an outbreak of severe pneumonia caused by the infection of SARS-CoV-2, a novel coronavirus first identified in Wuhan, China, imposes serious threats to public health. Upon infecting host cells, coronaviruses assemble a multi-subunit RNA-synthesis complex of viral non-structural proteins (nsp) responsible for the replication and transcription of the viral genome. Therefore, the role and inhibition of nsp12 are indispensable. A cryo-EM structure of RdRp from SARs-CoV-2 was used to identify novel drugs from Northern South African medicinal compounds database (NANPDB) by using computational virtual screening and molecular docking approaches. Considering Remdesivir as the control, 42 compounds were shortlisted to have docking score better than Remdesivir. The top 5 hits were validated by using molecular dynamics simulation approach and free energy calculations possess strong inhibitory properties than the Remdesivir. Thus, this study paved a way for designing novel drugs by decoding the architecture of an important enzyme and its inhibition with compounds from natural resources. This disclosing of necessary knowledge regarding the screening and the identification of top hits could help to design effective therapeutic candidates against the coronaviruses and design robust preventive measurements. GRAPHIC ABSTRACT: [Image: see text] Springer Berlin Heidelberg 2020-07-03 2020 /pmc/articles/PMC7332347/ /pubmed/32617855 http://dx.doi.org/10.1007/s12539-020-00381-9 Text en © International Association of Scientists in the Interdisciplinary Areas 2020 This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
spellingShingle Original Research Article
Khan, Abbas
Khan, Mazhar
Saleem, Shoaib
Babar, Zainib
Ali, Arif
Khan, Abdul Aziz
Sardar, Zain
Hamayun, Fahad
Ali, Syed Shujait
Wei, Dong-Qing
Phylogenetic Analysis and Structural Perspectives of RNA-Dependent RNA-Polymerase Inhibition from SARs-CoV-2 with Natural Products
title Phylogenetic Analysis and Structural Perspectives of RNA-Dependent RNA-Polymerase Inhibition from SARs-CoV-2 with Natural Products
title_full Phylogenetic Analysis and Structural Perspectives of RNA-Dependent RNA-Polymerase Inhibition from SARs-CoV-2 with Natural Products
title_fullStr Phylogenetic Analysis and Structural Perspectives of RNA-Dependent RNA-Polymerase Inhibition from SARs-CoV-2 with Natural Products
title_full_unstemmed Phylogenetic Analysis and Structural Perspectives of RNA-Dependent RNA-Polymerase Inhibition from SARs-CoV-2 with Natural Products
title_short Phylogenetic Analysis and Structural Perspectives of RNA-Dependent RNA-Polymerase Inhibition from SARs-CoV-2 with Natural Products
title_sort phylogenetic analysis and structural perspectives of rna-dependent rna-polymerase inhibition from sars-cov-2 with natural products
topic Original Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7332347/
https://www.ncbi.nlm.nih.gov/pubmed/32617855
http://dx.doi.org/10.1007/s12539-020-00381-9
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