Both Baicalein and Gallocatechin Gallate Effectively Inhibit SARS-CoV-2 Replication by Targeting M pro and Sepsis in Mice

The emergence of severe acute syndrome coronavirus 2 (SARS-CoV-2) in December 2019 has led to the global COVID-19 pandemic. Although the symptoms of most COVID-19 patients are mild or self-curable, most of severe patients have sepsis caused by cytokine storms, which greatly increases the case fatali...

Full description

Saved in:
Bibliographic Details
Published in:Inflammation 2022-06, Vol.45 (3), p.1076
Main Authors: Xiao, Ting, Cui, Mengqi, Zheng, Caijuan, Zhang, Peipei, Ren, Shanfa, Bao, Jiali, Gao, Dandi, Sun, Ronghao, Wang, Ming, Lin, Jianping, Zhang, Liang, Li, Mingjiang, Li, Dongmei, Zhou, Honggang, Yang, Cheng
Format: Article
Language:English
Subjects:
Animals
Antiviral Agents - chemistry
Antiviral Agents - pharmacology
Antiviral Agents - therapeutic use
Catechin - analogs & derivatives
Coronavirus 3C Proteases
COVID-19 - drug therapy
Cytokine Release Syndrome
Flavanones
Humans
Mice
Molecular Docking Simulation
Pandemics
Protease Inhibitors - pharmacology
SARS-CoV-2
Sepsis - drug therapy
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The emergence of severe acute syndrome coronavirus 2 (SARS-CoV-2) in December 2019 has led to the global COVID-19 pandemic. Although the symptoms of most COVID-19 patients are mild or self-curable, most of severe patients have sepsis caused by cytokine storms, which greatly increases the case fatality rate. Moreover, there is no effective drug that can limit the novel coronavirus thus far, so it is more needed to develop antiviral drugs for the SARS-CoV-2. In our research, we employed the techniques of molecular docking to screen 35 flavonoid compounds among which 29 compounds have Z-scores lower than - 6. Then, ( -)-gallocatechin gallate, ( +)-gallocatechin and baicalein were identified to have potent inhibitory activity against SARS-CoV-2 M with IC values of 5.774 ± 0.805 μM, 13.14 ± 2.081 μM and 5.158 ± 0.928 μM respectively by FRET assay. Molecular docking results also showed that ( -)-gallocatechin gallate, ( +)-gallocatechin and baicalein can non-covalently bind to M through π-π stacking and hydrogen bonds in the Cys145 catalytic site. We further evaluated the effect of ( -)-gallocatechin gallate and baicalein on cytokine storms using a mouse model of sepsis. ( -)-Gallocatechin gallate and baicalein significantly reduced sepsis of mouse models on weight, murine sepsis score, and survival rate and reduced the inflammatory factor levels, such as TNF-α, IL-1α, IL-4, and IL-10. Overall, ( -)-gallocatechin gallate and baicalein show certain potential of treatment against COVID-19.
ISSN:1573-2576