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

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 protei...

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Bibliographic Details
Published in:	Interdisciplinary sciences : computational life sciences Vol. 12; no. 3; pp. 335 - 348
Main Authors:	Khan, Abbas, Khan, Mazhar, Saleem, Shoaib, Babar, Zainib, Ali, Arif, Khan, Abdul Aziz, Sardar, Zain, Hamayun, Fahad, Ali, Syed Shujait, Wei, Dong-Qing
Format:	Journal Article
Language:	English
Published:	Berlin/Heidelberg Springer Berlin Heidelberg 01-09-2020 Springer Nature B.V
Subjects:	Adenosine Monophosphate - analogs & derivatives Adenosine Monophosphate - chemistry Adenosine Monophosphate - pharmacology Alanine - analogs & derivatives Alanine - chemistry Alanine - pharmacology Antiviral Agents - chemistry Antiviral Agents - pharmacology Betacoronavirus - drug effects Betacoronavirus - enzymology Betacoronavirus - genetics Biological Products - chemistry Biological Products - pharmacology Biomedical and Life Sciences Catalytic Domain - genetics Computational Biology/Bioinformatics Computational Science and Engineering Computer Appl. in Life Sciences Computer applications Computer Simulation Coronaviridae Coronavirus Infections - epidemiology Coronavirus Infections - virology Coronavirus RNA-Dependent RNA Polymerase Coronaviruses COVID-19 Databases, Pharmaceutical DNA-directed RNA polymerase Drug Evaluation, Preclinical Drugs Free energy Genome, Viral Genomes Health Sciences Host Microbial Interactions - drug effects Humans Life Sciences Ligands Mathematical and Computational Physics Medicine Molecular docking Molecular Docking Simulation Molecular dynamics Natural products Natural resources Original Original Research Article Pandemics Phylogeny Pneumonia, Viral - epidemiology Pneumonia, Viral - virology Public health Ribonucleic acid RNA RNA-Dependent RNA Polymerase - antagonists & inhibitors RNA-Dependent RNA Polymerase - chemistry RNA-Dependent RNA Polymerase - genetics SARS-CoV-2 Screening Severe acute respiratory syndrome coronavirus 2 Statistics for Life Sciences Structural proteins Theoretical Theoretical and Computational Chemistry Transcription Viral diseases Viral Nonstructural Proteins - antagonists & inhibitors Viral Nonstructural Proteins - chemistry Viral Nonstructural Proteins - genetics Phylogenetic Virtual screening SARs-CoV-2 Simulation RdRp Free energy
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Summary:	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
ISSN:	1913-2751 1867-1462
DOI:	10.1007/s12539-020-00381-9