Punicalagin as an allosteric NSP13 helicase inhibitor potently suppresses SARS-CoV-2 replication in vitro

Lu, Lian1; Peng, Yun2; Yao, Huiqiao1; Wang, Yanqun3; Li, Jinyu1; Yang, Yang2; Lin, Zhonghui1

2022-10-01

10.1016/j.antiviral.2022.105389

ANTIVIRAL RESEARCH   影响因子和分区

0166-3542

1872-9096

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) helicase NSP13 plays a conserved role in the replication of coronaviruses and has been identified as an ideal target for the development of antiviral drugs against SARS-CoV-2. Here, we identify a novel NSP13 helicase inhibitor punicalagin (PUG) through highthroughput screening. Surface plasmon resonance (SPR)-based analysis and molecular docking calculation reveal that PUG directly binds NSP13 on the interface of domains 1A and 2A, with a KD value of 21.6 nM. Further biochemical and structural analyses suggest that PUG inhibits NSP13 on ATP hydrolysis and prevents it binding to DNA substrates. Finally, the antiviral studies show that PUG effectively suppresses the SARS-CoV-2 replication in A549-ACE2 and Vero cells, with EC50 values of 347 nM and 196 nM, respectively. Our work demonstrates the potential application of PUG in the treatment of coronavirus disease 2019 (COVID-19) and identifies an allosteric inhibition mechanism for future drug design targeting the viral helicases.

SARS-CoV-2 NSP13 Helicase Inhibitor Punicalagin

SCI

英语

通讯

National Natural Science Foundation of China["31971222","32170936","22173020"]

Pharmacology & Pharmacy ; Virology

Pharmacology & Pharmacy ; Virology

WOS:000850800900002

ELSEVIER

PHARMACOLOGY & TOXICOLOGY

Web of Science

1.Fuzhou Univ, Coll Chem, Fuzhou 350108, Peoples R China
2.Southern Univ Sci & Technol, Shenzhen Peoples Hosp 3, Natl Clin Res Ctr Infect Dis,Second Hosp 2, Shenzhen Key Lab Pathogen & Immun,State Key Discip, Shenzhen, Peoples R China
3.Guangzhou Med Univ, Guangzhou Inst Resp Hlth, Natl Clin Res Ctr Resp Dis, State Key Lab Resp Dis,Affiliated Hosp 1, Guangzhou 510182, Guangdong, Peoples R China

Lu, Lian,Peng, Yun,Yao, Huiqiao,et al. Punicalagin as an allosteric NSP13 helicase inhibitor potently suppresses SARS-CoV-2 replication in vitro[J]. ANTIVIRAL RESEARCH,2022,206.

Lu, Lian.,Peng, Yun.,Yao, Huiqiao.,Wang, Yanqun.,Li, Jinyu.,...&Lin, Zhonghui.(2022).Punicalagin as an allosteric NSP13 helicase inhibitor potently suppresses SARS-CoV-2 replication in vitro.ANTIVIRAL RESEARCH,206.

Lu, Lian,et al."Punicalagin as an allosteric NSP13 helicase inhibitor potently suppresses SARS-CoV-2 replication in vitro".ANTIVIRAL RESEARCH 206(2022).