Article ; Online: Pharmacoinformatics approach based identification of potential Nsp15 endoribonuclease modulators for SARS-CoV-2 inhibition.
Archives of biochemistry and biophysics
2021 Volume 700, Page(s) 108771
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- ... ...
| 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. |
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| MeSH term(s) | Antiviral Agents/chemistry ; Antiviral Agents/pharmacokinetics ; Antiviral Agents/pharmacology ; COVID-19/drug therapy ; COVID-19/metabolism ; COVID-19/virology ; Databases, Chemical ; Drug Evaluation, Preclinical ; Endoribonucleases/antagonists & inhibitors ; Endoribonucleases/chemistry ; Enzyme Inhibitors/chemistry ; Enzyme Inhibitors/pharmacokinetics ; Enzyme Inhibitors/pharmacology ; Humans ; In Vitro Techniques ; Ligands ; Molecular Docking Simulation ; Molecular Dynamics Simulation ; Molecular Structure ; SARS-CoV-2/drug effects ; SARS-CoV-2/enzymology ; User-Computer Interface ; Viral Nonstructural Proteins/antagonists & inhibitors ; Viral Nonstructural Proteins/chemistry |
| Chemical Substances | Antiviral Agents ; Enzyme Inhibitors ; Ligands ; Viral Nonstructural Proteins ; Endoribonucleases (EC 3.1.-) ; nidoviral uridylate-specific endoribonuclease (EC 3.1.-) |
| Language | English |
| Publishing date | 2021-01-21 |
| Publishing country | United States |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 523-x |
| ISSN | 1096-0384 ; 0003-9861 |
| ISSN (online) | 1096-0384 |
| ISSN | 0003-9861 |
| DOI | 10.1016/j.abb.2021.108771 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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