國家衛生研究院 NHRI:Item 3990099045/14200

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Title:	Identification of entry inhibitors against delta and omicron variants of SARS-CoV-2
Authors:	Lee, RKL;Li, TN;Chang, SY;Chao, TL;Kuo, CH;Pan, MYC;Chiou, YT;Liao, KJ;Yang, Y;Wu, YH;Huang, CH;Juan, HF;Hsieh, HP;Wang, LHC
Contributors:	Institute of Biotechnology and Pharmaceutical Research
Abstract:	Entry inhibitors against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are urgently needed to control the outbreak of coronavirus disease 2019 (COVID-19). This study developed a robust and straightforward assay that detected the molecular interaction between the receptor-binding domain (RBD) of viral spike protein and the angiotensin-converting enzyme 2 (ACE2) receptor in just 10 min. A drug library of 1068 approved compounds was used to screen for SARS-CoV2 entry inhibition, and 9 active drugs were identified as specific pseudovirus entry inhibitors. A plaque reduction neutralization test using authentic SARS-CoV-2 virus in Vero E6 cells confirmed that 2 of these drugs (Etravirine and Dolutegravir) significantly inhibited the infection of SARS-CoV-2. With molecular docking, we showed that both Etravirine and Dolutegravir are preferentially bound to primary ACE2-interacting residues on the RBD domain, implying that these two drug blocks may prohibit the viral attachment of SARS-CoV-2. We compared the neutralizing activities of these entry inhibitors against different pseudoviruses carrying spike proteins from alpha, beta, gamma, and delta variants. Both Etravirine and Dolutegravir showed similar neutralizing activities against different variants, with EC50 values between 4.5 to 5.8 nM for Etravirine and 10.2 to 22.9 nM for Dolutegravir. These data implied that Etravirine and Dolutegravir may serve as general spike inhibitors against dominant viral variants of SARS-CoV-2.
Date:	2022-04-06
Relation:	International Journal of Molecular Sciences. 2022 Apr 6;23(7):Article number 4050.
Link to:	http://dx.doi.org/10.3390/ijms23074050
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1422-0067&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000781421100001
Cited Times(Scopus):	https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85127574749
Appears in Collections:	[Hsing-Pang Hsieh] Periodical Articles

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