1. Accelerated Discovery of Potent Fusion Inhibitors for Respiratory Syncytial Virus
- Author
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Perry W. Bartsch, Julien Sourimant, Thalia Le, Edgars Jecs, Nicole Pribut, Richard K. Plemper, Stephen C. Pelly, Robert Wilson, Zackery W. Dentmon, Savita Sharma, Pieter B. Burger, Jeong-Joong Yoon, Dennis C. Liotta, Thomas M. Kaiser, and Soyon S. Hwang
- Subjects
0301 basic medicine ,Fusion ,Benzimidazole ,030106 microbiology ,Antiviral Agents ,Fusion protein ,Article ,Virus ,In vitro ,Structure-Activity Relationship ,03 medical and health sciences ,chemistry.chemical_compound ,030104 developmental biology ,Infectious Diseases ,Biochemistry ,chemistry ,Respiratory Syncytial Virus, Human ,Potency ,Benzimidazoles ,Respiratory system ,Viral Fusion Proteins ,EC50 - 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 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.
- Published
- 2020
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