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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...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Berlin Heidelberg
2020
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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] |
format | Online Article Text |
id | pubmed-7332347 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
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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