中文版 | English
Title

A Retinol Derivative Inhibits SARS-CoV-2 Infection by Interrupting Spike-Mediated Cellular Entry

Author
Corresponding AuthorLi, Liang; Zhang, Renli; Xiang, Ye; Cheng, Gong
Publication Years
2022-07-01
DOI
Source Title
ISSN
2150-7511
Abstract

["Retinoids, a group of compounds including vitamin A and its active metabolite all-trans retinoic acid (ATRA), regulate serial physiological activity in multiple organ systems, such as cell growth, differentiation, and apoptosis. The ATRA analogues reported to date include more than 4,000 natural and synthetic molecules that are structurally and/or functionally related to ATRA.","Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent of the global pandemic and life-threatening coronavirus disease 2019 (COVID-19). Although vaccines and therapeutic antibodies are available, their efficacy is continuously undermined by rapidly emerging SARS-CoV-2 variants. Here, we found that all-trans retinoic acid (ATRA), a vitamin A (retinol) derivative, showed potent antiviral activity against all SARS-CoV-2 variants in both human cell lines and human organoids of the lower respiratory tract. Mechanistically, ATRA directly binds in a deep hydrophobic pocket of the receptor binding domain (RBD) located on the top of the SARS-CoV-2 spike protein (S) trimer. The bound ATRA mediates strong interactions between the \"down\" RBDs and locks most of the S trimers in an RBD \"all-down\" and ACE2-inaccessible inhibitory conformation. In summary, our results reveal the pharmacological biotargets and structural mechanism of ATRA and other retinoids in SARS-CoV-2 infection and suggest that ATRA and its derivatives could be potential hit compounds against a broad spectrum of coronaviruses. IMPORTANCE Retinoids, a group of compounds including vitamin A and its active metabolite all-trans retinoic acid (ATRA), regulate serial physiological activity in multiple organ systems, such as cell growth, differentiation, and apoptosis. The ATRA analogues reported to date include more than 4,000 natural and synthetic molecules that are structurally and/or functionally related to ATRA. Here, we found that ATRA showed potent antiviral activity against all SARS-CoV-2 variants by directly binding in a deep hydrophobic pocket of the receptor binding domain (RBD) located on top of the SARS-CoV-2 spike protein (S) trimer. The bound ATRA mediates strong interactions between the \"down\" RBDs and locks most of the S trimers in an RBD \"all-down\" and ACE2-inaccessible inhibitory conformation, suggesting the pharmacological feasibility of using ATRA or its derivatives as a remedy for and prevention of COVID-19 disease."]

Keywords
URL[Source Record]
Indexed By
Language
English
SUSTech Authorship
Corresponding
Funding Project
National Key Research and Development Plan of China[
WOS Research Area
Microbiology
WOS Subject
Microbiology
WOS Accession No
WOS:000825310400003
Publisher
Data Source
Web of Science
Citation statistics
Cited Times [WOS]:5
Document TypeJournal Article
Identifierhttp://kc.sustech.edu.cn/handle/2SGJ60CL/356162
DepartmentSchool of Medicine
南方科技大学医学院_药理学系
Affiliation
1.Tsinghua Univ, Sch Med, Tsinghua Peking Joint Ctr Life Sci, Beijing Frontier Res Ctr Biol Struct, Beijing, Peoples R China
2.Tsinghua Univ, Sch Med, Beijing Adv Innovat Ctr Struct Biol, Beijing, Peoples R China
3.Shenzhen Bay Lab, Inst Infect Dis, Shenzhen, Guangdong, Peoples R China
4.Sun Yat Sen Univ, Dept Otolaryngol, Affiliated Hosp 7, Shenzhen, Peoples R China
5.Sun Yat Sen Univ, Dept Thorac Surg, Affiliated Hosp 7, Shenzhen, Peoples R China
6.Shenzhen Ctr Dis Control & Prevent, Inst Pathogen Organisms, Shenzhen, Guangdong, Peoples R China
7.Southern Univ Sci & Technol, Sch Med, Dept Pharmacol, Shenzhen, Peoples R China
8.Chinese Acad Sci, Shenzhen Inst Adv Technol, Shenzhen, Guangdong, Peoples R China
9.Univ Connecticut Hlth Ctr, Sch Med, Dept Immunol, Farmington, CT USA
Corresponding Author AffilicationSchool of Medicine
Recommended Citation
GB/T 7714
Tong, Liangqin,Wang, Lin,Liao, Shumin,et al. A Retinol Derivative Inhibits SARS-CoV-2 Infection by Interrupting Spike-Mediated Cellular Entry[J]. mBio,2022.
APA
Tong, Liangqin.,Wang, Lin.,Liao, Shumin.,Xiao, Xiaoping.,Qu, Jing.,...&Cheng, Gong.(2022).A Retinol Derivative Inhibits SARS-CoV-2 Infection by Interrupting Spike-Mediated Cellular Entry.mBio.
MLA
Tong, Liangqin,et al."A Retinol Derivative Inhibits SARS-CoV-2 Infection by Interrupting Spike-Mediated Cellular Entry".mBio (2022).
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