Investigation of small molecule inhibitors of the SARS-CoV-2 papain-like protease by all-atom microsecond modelling, PELE Monte Carlo simulations, and in vitro activity inhibition
Visualitza/Obre
10.1016/j.cplett.2021.139294
Inclou dades d'ús des de 2022
Cita com:
hdl:2117/367571
Tipus de documentArticle
Data publicació2022
EditorElsevier
Condicions d'accésAccés obert
Llevat que s'hi indiqui el contrari, els
continguts d'aquesta obra estan subjectes a la llicència de Creative Commons
:
Reconeixement-NoComercial-SenseObraDerivada 3.0 Espanya
Abstract
The SARS-CoV-2 papain-like (PLpro) protease is essential for viral replication. We investigated potential antiviral effects of hypericin relative to the well-known noncovalent PLpro inhibitor GRL-0617. Molecular dynamics and PELE Monte Carlo simulations highlight favourable binding of hypericin and GRL-0617 to the naphthalene binding pocket of PLpro. Although not potent as GRL-0617 (45.8 vs 1.6 µM for protease activity, respectively), in vitro fluorogenic enzymatic assays with hypericin show concentration-dependent inhibition of both PLpro protease and deubiquitinating activities. Given its use in supplementations and the FDA conditional approval of a synthetic version, further evaluation of hypericin as a potential SARS-CoV-2 antiviral is warranted.
CitacióLiang, J.J. [et al.]. Investigation of small molecule inhibitors of the SARS-CoV-2 papain-like protease by all-atom microsecond modelling, PELE Monte Carlo simulations, and in vitro activity inhibition. "Chemical Physics Letters", 2022, vol. 788, 139294.
ISSN0009-2614
Versió de l'editorhttps://www.sciencedirect.com/science/article/pii/S0009261421009775
Col·leccions
Fitxers | Descripció | Mida | Format | Visualitza |
---|---|---|---|---|
Liang et al_PLpro AAM.pdf | 949,3Kb | Visualitza/Obre |