南方科技大学知识苑(SUSTech KC): Punicalagin as an allosteric NSP13 helicase inhibitor potently suppresses SARS-CoV-2 replication in vitro

Title	Punicalagin as an allosteric NSP13 helicase inhibitor potently suppresses SARS-CoV-2 replication in vitro
Author	Lu, Lian 1; Peng, Yun 2; Yao, Huiqiao 1; Wang, Yanqun 3; Li, Jinyu 1; Yang, Yang 2 ; Lin, Zhonghui 1
Corresponding Author	Li, Jinyu; Yang, Yang; Lin, Zhonghui
Publication Years	2022-10-01
DOI	10.1016/j.antiviral.2022.105389
Source Title	ANTIVIRAL RESEARCH Impact Factor & Quartile
ISSN	0166-3542
EISSN	1872-9096
Volume	206
Abstract	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.
Keywords	SARS-CoV-2 NSP13 Helicase Inhibitor Punicalagin
URL	[Source Record]
Indexed By	SCI
Language	English
SUSTech Authorship	Corresponding
Funding Project	National Natural Science Foundation of China["31971222","32170936","22173020"]
WOS Research Area	Pharmacology & Pharmacy ; Virology
WOS Subject	Pharmacology & Pharmacy ; Virology
WOS Accession No	WOS:000850800900002
Publisher	ELSEVIER
ESI Research Field	PHARMACOLOGY & TOXICOLOGY
Data Source	Web of Science
Citation statistics	Cited Times [WOS]:2
Document Type	Journal Article
Identifier	http://kc.sustech.edu.cn/handle/2SGJ60CL/395912
Department	The Third People's Hospital of Shenzhen 南方科技大学第一附属医院
Affiliation	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
Corresponding Author Affilication	The Third People's Hospital of Shenzhen; Shenzhen People's Hospital
Recommended Citation GB/T 7714	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.
APA	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.
MLA	Lu, Lian,et al."Punicalagin as an allosteric NSP13 helicase inhibitor potently suppresses SARS-CoV-2 replication in vitro".ANTIVIRAL RESEARCH 206(2022).

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