Licorice-saponin A3 is a broad-spectrum inhibitor for COVID-19 by targeting viral spike and anti-inflammation
10.1016/j.jpha.2023.05.011
- Author:
Yang YI
1
;
Wenzhe LI
;
Kefang LIU
;
Heng XUE
;
Rong YU
;
Meng ZHANG
;
Yang-Oujie BAO
;
Xinyuan LAI
;
Jingjing FAN
;
Yuxi HUANG
;
Jing WANG
;
Xiaomeng SHI
;
Junhua LI
;
Hongping WEI
;
Kuanhui XIANG
;
Linjie LI
;
Rong ZHANG
;
Xin ZHAO
;
Xue QIAO
;
Hang YANG
;
Min YE
Author Information
1. State Key Laboratory of Natural and Biomimetic Drugs,School of Pharmaceutical Sciences,Peking University,Beijing,100191,China
- Keywords:
COVID-19;
Inflammation;
Licorice-saponin A3;
Receptor-binding domain(RBD);
SARS-CoV-2
- From:
Journal of Pharmaceutical Analysis
2024;14(1):115-127
- CountryChina
- Language:Chinese
-
Abstract:
Currently,human health due to corona virus disease 2019(COVID-19)pandemic has been seriously threatened.The coronavirus severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)spike(S)protein plays a crucial role in virus transmission and several S-based therapeutic approaches have been approved for the treatment of COVID-19.However,the efficacy is compromised by the SARS-CoV-2 evolvement and mutation.Here we report the SARS-CoV-2 S protein receptor-binding domain(RBD)inhibitor licorice-saponin A3(A3)could widely inhibit RBD of SARS-CoV-2 variants,including Beta,Delta,and Omicron BA.1,XBB and BQ1.1.Furthermore,A3 could potently inhibit SARS-CoV-2 Omicron virus in Vero E6 cells,with EC50 of 1.016 pM.The mechanism was related to binding with Y453 of RBD deter-mined by hydrogen-deuterium exchange mass spectrometry(HDX-MS)analysis combined with quan-tum mechanics/molecular mechanics(QM/MM)simulations.Interestingly,phosphoproteomics analysis and multi fluorescent immunohistochemistry(mIHC)respectively indicated that A3 also inhibits host inflammation by directly modulating the JNK and p38 mitogen-activated protein kinase(MAPK)path-ways and rebalancing the corresponding immune dysregulation.This work supports A3 as a promising broad-spectrum small molecule drug candidate for COVID-19.
