Accelerated Discovery of Potent Fusion Inhibitors for Respiratory Syncytial Virus
Nicole Pribut, Thomas M. Kaiser, Robert J. Wilson, Edgars Jēčs, Zackery W. Dentmon, Stephen C. Pelly, Savita K. Sharma, Perry W. Bartsch, Pieter B. Burger, Soyon S. Hwang, Thalia Le, Julien Sourimant, Jeong-Joong Yoon, Richard K. Plemper, Dennis C. Liotta
Abstract
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 EC50 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 EC50 value of 0.5 nM.
Topics & Concepts
EC50PotencyBenzimidazoleDrug discoveryVirusIn vitroRespiratory systemMononegaviralesParamyxoviridaeFusionVirologyChemistryBiochemistryCombinatorial chemistryBiologyViral diseaseOrganic chemistryPhilosophyAnatomyLinguisticsRespiratory viral infections researchPneumonia and Respiratory InfectionsInfluenza Virus Research Studies