Pharmacoinformatics approach based identification of potential Nsp15 endoribonuclease modulators for SARS-CoV-2 inhibition

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dc.contributor.author Savale, Rutuja Umesh
dc.contributor.author Bhowmick, Shovonlal
dc.contributor.author Osman, Sameh Mohamed
dc.contributor.author Alasmary, Fatmah Ali
dc.contributor.author Almutairi, Tahani Mazyad
dc.contributor.author Abdullah, Dalal Saied
dc.contributor.author Patil, Pritee Chunarkar
dc.contributor.author Islam, Md Ataul
dc.date.accessioned 2022-08-26T07:56:07Z
dc.date.available 2022-08-26T07:56:07Z
dc.date.issued 2021-03
dc.description.abstract In the current study, a structure-based virtual screening paradigm was used to screen a small molecular database against the Non-structural protein 15 (Nsp15) endoribonuclease of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The SARS-CoV-2 is the causative agent of the recent outbreak of coronavirus disease 2019 (COVID-19) which left the entire world locked down inside the home. A multi-step molecular docking study was performed against antiviral specific compounds (~8722) collected from the Asinex antiviral database. The less or non-interacting molecules were wiped out sequentially in the molecular docking. Further, MM-GBSA based binding free energy was estimated for 26 compounds which shows a high affinity towards the Nsp15. The drug-likeness and pharmacokinetic parameters of all 26 compounds were explored, and five molecules were found to have an acceptable pharmacokinetic profile. Overall, the Glide-XP docking score and Prime-MM-GBSA binding free energy of the selected molecules were explained strong interaction potentiality towards the Nsp15 endoribonuclease. The dynamic behavior of each molecule with Nsp15 was assessed using conventional molecular dynamics (MD) simulation. The MD simulation information was strongly favors the Nsp15 and each identified ligand stability in dynamic condition. Finally, from the MD simulation trajectories, the binding free energy was estimated using the MM-PBSA method. Hence, the proposed final five molecules might be considered as potential Nsp15 modulators for SARS-CoV-2 inhibition. en_US
dc.description.department Chemical Pathology en_US
dc.description.librarian hj2022 en_US
dc.description.sponsorship The Deanship of Scientific Research at King Saud University en_US
dc.description.uri https://www.elsevier.com/locate/yabbi en_US
dc.identifier.citation Savale, R.U., Bhowmick, S., Osman, S.M. et al. 2021, 'Pharmacoinformatics approach based identification of potential Nsp15 endoribonuclease modulators for SARS-CoV-2 inhibition', Archives of Biochemistry and Biophysics, vol. 700, art. 108771, pp. 1-13, doi : 10.1016/j.abb.2021.108771. en_US
dc.identifier.issn 0003-9861 (print)
dc.identifier.issn 1096-0384 (online)
dc.identifier.other 10.1016/j.abb.2021.108771
dc.identifier.uri https://repository.up.ac.za/handle/2263/86972
dc.language.iso en en_US
dc.publisher Elsevier en_US
dc.rights © 2021 Elsevier Inc. All rights reserved. Notice : this is the author’s version of a work that was accepted for publication in Archives of Biochemistry and Biophysics. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. A definitive version was subsequently published in Archives of Biochemistry and Biophysics, vol. 700, art. 108771, pp. 1-13, 2021. doi : 10.1016/j.abb.2021.108771. en_US
dc.subject Nsp15 endoribonuclease en_US
dc.subject Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) en_US
dc.subject Coronavirus disease 2019 (COVID-19) en_US
dc.subject COVID-19 pandemic en_US
dc.subject Virtual screening en_US
dc.subject Molecular dynamics en_US
dc.subject.other Health sciences articles SDG-03
dc.subject.other SDG-03: Good health and well-being
dc.title Pharmacoinformatics approach based identification of potential Nsp15 endoribonuclease modulators for SARS-CoV-2 inhibition en_US
dc.type Postprint Article en_US


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