The inhibitory effects of PGG and EGCG against the SARS-CoV-2 3C-like protease

Autor: Hsin Yi Yang, Yi Shuan Lyu, Jui Chieh Chen, Yun Ti Chen, Lih Hwa Hwang, Wei Chung Chiou, Jinn-Moon Yang, Cheng Huang
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Models
Molecular
0301 basic medicine
Molecular model
viruses
medicine.medical_treatment
Drug Evaluation
Preclinical
Biophysics
Peptide
Virus Replication
Cleavage (embryo)
medicine.disease_cause
Biochemistry
Catechin
Article
Virus
03 medical and health sciences
0302 clinical medicine
Protein Domains
medicine
Humans
Protease Inhibitors
skin and connective tissue diseases
Pandemics
Molecular Biology
Coronavirus 3C Proteases
Coronavirus
chemistry.chemical_classification
Binding Sites
Protease
Molecular Structure
PGG
SARS-CoV-2
Chemistry
fungi
COVID-19
virus diseases
Cell Biology
Hydrolyzable Tannins
Molecular Docking Simulation
body regions
Kinetics
030104 developmental biology
Förster resonance energy transfer
3CL protease (3CLpro)
Viral replication
030220 oncology & carcinogenesis
EGCG
Protein Binding
Zdroj: Biochemical and Biophysical Research Communications
ISSN: 0006-291X
DOI: 10.1016/j.bbrc.2020.12.106
Popis: 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 Vmax 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.
Graphical abstract Image 1
Highlights • An effective SARS-CoV-2 3CLpro inhibitor is imperative for COVID-19 treatment. • The Vmax of SARS-CoV-2 3CLpro was about 2-fold higher than that of SARS-CoV 3CLpro. • PGG and EGCG show potent inhibitory activity against SARS-CoV-2 3CLpro. • PGG and EGCG strongly interact with the catalytic sites of SARS-CoV-2 3CLpro. • PGG and EGCG possess therapeutic potentials for treating SARS-CoV-2 infection.
Databáze: OpenAIRE
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