Accelerated Discovery of Potent Fusion Inhibitors for Respiratory Syncytial Virus.

Autor:	Pribut N; Department of Chemistry, Emory University, 1515 Dickey Drive, Atlanta, Georgia 30322, United States., Kaiser TM; Department of Chemistry, Emory University, 1515 Dickey Drive, Atlanta, Georgia 30322, United States., Wilson RJ; Department of Chemistry, Emory University, 1515 Dickey Drive, Atlanta, Georgia 30322, United States., Jecs E; Department of Chemistry, Emory University, 1515 Dickey Drive, Atlanta, Georgia 30322, United States., Dentmon ZW; Department of Chemistry, Emory University, 1515 Dickey Drive, Atlanta, Georgia 30322, United States., Pelly SC; Department of Chemistry, Emory University, 1515 Dickey Drive, Atlanta, Georgia 30322, United States., Sharma S; Department of Chemistry, Emory University, 1515 Dickey Drive, Atlanta, Georgia 30322, United States., Bartsch PW 3rd; Department of Chemistry, Emory University, 1515 Dickey Drive, Atlanta, Georgia 30322, United States., Burger PB; Department of Chemistry, Emory University, 1515 Dickey Drive, Atlanta, Georgia 30322, United States., Hwang SS; Department of Chemistry, Emory University, 1515 Dickey Drive, Atlanta, Georgia 30322, United States., Le T; Department of Chemistry, Emory University, 1515 Dickey Drive, Atlanta, Georgia 30322, United States., Sourimant J; Institute for Biomedical Sciences, Georgia State University, Atlanta, Georgia 30303, United States., Yoon JJ; Institute for Biomedical Sciences, Georgia State University, Atlanta, Georgia 30303, United States., Plemper RK; Institute for Biomedical Sciences, Georgia State University, Atlanta, Georgia 30303, United States., Liotta DC; Department of Chemistry, Emory University, 1515 Dickey Drive, Atlanta, Georgia 30322, United States.
Jazyk:	angličtina
Zdroj:	ACS infectious diseases [ACS Infect Dis] 2020 May 08; Vol. 6 (5), pp. 922-929. Date of Electronic Publication: 2020 Apr 20.
DOI:	10.1021/acsinfecdis.9b00524
Abstrakt:	A series of five benzimidazole-based compounds were identified using a machine learning algorithm as potential inhibitors of the respiratory syncytial virus (RSV) fusion protein. These compounds were synthesized, and compound 2 in particular exhibited excellent in vitro potency with an EC 50 value of 5 nM. This new scaffold was then further refined leading to the identification of compound 44 , which exhibited a 10-fold improvement in activity with an EC 50 value of 0.5 nM.
Databáze:	MEDLINE
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