Biochem Biophys Res Commun . The inhibitory effects of PGG and EGCG against the SARS-CoV-2 3C-like protease

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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 ¹ , Jui-Chieh Chen ² , Yun-Ti Chen ³ , Jinn-Moon Yang ⁴ , Lih-Hwa Hwang ⁵ , Yi-Shuan Lyu ¹ , Hsin-Yi Yang ¹ , Cheng Huang ⁶



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_max 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.