tetano
Editor, Senior Moderator
Chem Phys Lett
. 2021 Dec 18;139294.
doi: 10.1016/j.cplett.2021.139294. Online ahead of print.
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
Julia J Liang[SUP] 1 2 [/SUP], Eleni Pitsillou[SUP] 1 2 [/SUP], Katherine Ververis[SUP] 1 [/SUP], Victor Guallar[SUP] 3 4 [/SUP], Andrew Hung[SUP] 2 [/SUP], Tom C Karagiannis[SUP] 1 5 [/SUP]
Affiliations
Abstract
The SARS-CoV-2 papain-like (PL[SUP]pro[/SUP]) protease is essential for viral replication. We investigated potential antiviral effects of hypericin relative to the well-known noncovalent PL[SUP]pro[/SUP] inhibitor GRL-0617. Molecular dynamics and PELE Monte Carlo simulations highlight favourable binding of hypericin and GRL-0617 to the naphthalene binding pocket of PL[SUP]pro[/SUP]. Although not potent as GRL-0617 (45.8 vs 1.6µM for protease activity, respectively), in vitro fluorogenic enzymatic assays with hypericin show concentration-dependent inhibition of both PL[SUP]pro[/SUP] 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.
Keywords: COVID-19; Coronavirus; GRL0617; SARS-CoV-2; hypericin; molecular modelling; papain-like protease.
. 2021 Dec 18;139294.
doi: 10.1016/j.cplett.2021.139294. Online ahead of print.
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
Julia J Liang[SUP] 1 2 [/SUP], Eleni Pitsillou[SUP] 1 2 [/SUP], Katherine Ververis[SUP] 1 [/SUP], Victor Guallar[SUP] 3 4 [/SUP], Andrew Hung[SUP] 2 [/SUP], Tom C Karagiannis[SUP] 1 5 [/SUP]
Affiliations
- PMID: 34961797
- PMCID: PMC8693950
- DOI: 10.1016/j.cplett.2021.139294
Abstract
The SARS-CoV-2 papain-like (PL[SUP]pro[/SUP]) protease is essential for viral replication. We investigated potential antiviral effects of hypericin relative to the well-known noncovalent PL[SUP]pro[/SUP] inhibitor GRL-0617. Molecular dynamics and PELE Monte Carlo simulations highlight favourable binding of hypericin and GRL-0617 to the naphthalene binding pocket of PL[SUP]pro[/SUP]. Although not potent as GRL-0617 (45.8 vs 1.6µM for protease activity, respectively), in vitro fluorogenic enzymatic assays with hypericin show concentration-dependent inhibition of both PL[SUP]pro[/SUP] 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.
Keywords: COVID-19; Coronavirus; GRL0617; SARS-CoV-2; hypericin; molecular modelling; papain-like protease.