Savale, Rutuja UmeshBhowmick, ShovonlalOsman, Sameh MohamedAlasmary, Fatmah AliAlmutairi, Tahani MazyadAbdullah, Dalal SaiedPatil, Pritee ChunarkarIslam, Md Ataul2022-08-262022-08-262021-03Savale, 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.2021.108771.0003-9861 (print)1096-0384 (online)10.1016/j.abb.2021.108771https://repository.up.ac.za/handle/2263/86972In 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© 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.Nsp15 endoribonucleaseSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2)Coronavirus disease 2019 (COVID-19)COVID-19 pandemicVirtual screeningMolecular dynamicsHealth sciences articles SDG-03SDG-03: Good health and well-beingPostprint Article