tetano
Editor, Senior Moderator
Biochem Biophys Res Commun
. 2021 Jan 6;S0006-291X(20)32299-3.
doi: 10.1016/j.bbrc.2020.12.106. Online ahead of print.
The inhibitory effects of PGG and EGCG against the SARS-CoV-2 3C-like protease
Wei-Chung Chiou[SUP] 1 [/SUP], Jui-Chieh Chen[SUP] 2 [/SUP], Yun-Ti Chen[SUP] 3 [/SUP], Jinn-Moon Yang[SUP] 4 [/SUP], Lih-Hwa Hwang[SUP] 5 [/SUP], Yi-Shuan Lyu[SUP] 1 [/SUP], Hsin-Yi Yang[SUP] 1 [/SUP], Cheng Huang[SUP] 6 [/SUP]
Affiliations
Abstract
The coronavirus disease (COVID-19) pandemic, resulting from human-to-human transmission of a novel severe acute respiratory syndrome coronavirus (SARS-CoV-2), has led to a global health crisis. Given that the 3 chymotrypsin-like protease (3CLpro) of SARS-CoV-2 plays an indispensable role in viral polyprotein processing, its successful inhibition halts viral replication and thus constrains virus spread. Therefore, developing an effective SARS-CoV-2 3CLpro inhibitor to treat COVID-19 is imperative. A fluorescence resonance energy transfer (FRET)-based method was used to assess the proteolytic activity of SARS-CoV-2 3CLpro using intramolecularly quenched fluorogenic peptide substrates corresponding to the cleavage sequence of SARS-CoV-2 3CLpro. Molecular modeling with GEMDOCK was used to simulate the molecular interactions between drugs and the binding pocket of SARS-CoV-2 3CLpro. This study revealed that the V[SUB]max[/SUB] of SARS-CoV-2 3CLpro was about 2-fold higher than that of SARS-CoV 3CLpro. Interestingly, the proteolytic activity of SARS-CoV-2 3CLpro is slightly more efficient than that of SARS-CoV 3CLpro. Meanwhile, natural compounds PGG and EGCG showed remarkable inhibitory activity against SARS-CoV-2 3CLpro than against SARS-CoV 3CLpro. In molecular docking, PGG and EGCG strongly interacted with the substrate binding pocket of SARS-CoV-2 3CLpro, forming hydrogen bonds with multiple residues, including the catalytic residues C145 and H41. The activities of PGG and EGCG against SARS-CoV-2 3CLpro demonstrate their inhibition of viral protease activity and highlight their therapeutic potentials for treating SARS-CoV-2 infection.
Keywords: 3CL protease (3CLpro); COVID-19; EGCG; PGG; SARS-CoV-2.
. 2021 Jan 6;S0006-291X(20)32299-3.
doi: 10.1016/j.bbrc.2020.12.106. Online ahead of print.
The inhibitory effects of PGG and EGCG against the SARS-CoV-2 3C-like protease
Wei-Chung Chiou[SUP] 1 [/SUP], Jui-Chieh Chen[SUP] 2 [/SUP], Yun-Ti Chen[SUP] 3 [/SUP], Jinn-Moon Yang[SUP] 4 [/SUP], Lih-Hwa Hwang[SUP] 5 [/SUP], Yi-Shuan Lyu[SUP] 1 [/SUP], Hsin-Yi Yang[SUP] 1 [/SUP], Cheng Huang[SUP] 6 [/SUP]
Affiliations
- PMID: 33454058
- DOI: 10.1016/j.bbrc.2020.12.106
Abstract
The coronavirus disease (COVID-19) pandemic, resulting from human-to-human transmission of a novel severe acute respiratory syndrome coronavirus (SARS-CoV-2), has led to a global health crisis. Given that the 3 chymotrypsin-like protease (3CLpro) of SARS-CoV-2 plays an indispensable role in viral polyprotein processing, its successful inhibition halts viral replication and thus constrains virus spread. Therefore, developing an effective SARS-CoV-2 3CLpro inhibitor to treat COVID-19 is imperative. A fluorescence resonance energy transfer (FRET)-based method was used to assess the proteolytic activity of SARS-CoV-2 3CLpro using intramolecularly quenched fluorogenic peptide substrates corresponding to the cleavage sequence of SARS-CoV-2 3CLpro. Molecular modeling with GEMDOCK was used to simulate the molecular interactions between drugs and the binding pocket of SARS-CoV-2 3CLpro. This study revealed that the V[SUB]max[/SUB] of SARS-CoV-2 3CLpro was about 2-fold higher than that of SARS-CoV 3CLpro. Interestingly, the proteolytic activity of SARS-CoV-2 3CLpro is slightly more efficient than that of SARS-CoV 3CLpro. Meanwhile, natural compounds PGG and EGCG showed remarkable inhibitory activity against SARS-CoV-2 3CLpro than against SARS-CoV 3CLpro. In molecular docking, PGG and EGCG strongly interacted with the substrate binding pocket of SARS-CoV-2 3CLpro, forming hydrogen bonds with multiple residues, including the catalytic residues C145 and H41. The activities of PGG and EGCG against SARS-CoV-2 3CLpro demonstrate their inhibition of viral protease activity and highlight their therapeutic potentials for treating SARS-CoV-2 infection.
Keywords: 3CL protease (3CLpro); COVID-19; EGCG; PGG; SARS-CoV-2.