Screening and Identification of Lassa Virus Entry Inhibitors from an FDA-Approved Drug Library

Author:

Wang Peilin12,Liu Yang2,Zhang Guangshun3,Wang Shaobo12,Guo Jiao12,Cao Junyuan12,Jia Xiaoying12,Zhang Leike12,Xiao Gengfu12,Wang Wei12

Affiliation:

1. University of the Chinese Academy of Sciences, Beijing, China

2. State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China

3. College of Pharmacy and State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, China

Abstract

Currently, there is no approved therapy to treat Lassa fever; therefore, repurposing of approved drugs will accelerate the development of a therapeutic stratagem. In this study, we screened an FDA-approved library of drugs and identified two compounds, lacidipine and phenothrin, which inhibited Lassa virus entry by blocking low-pH-induced membrane fusion. Additionally, both compounds extended their inhibition against the entry of Guanarito virus, and the viral targets were identified as the SSP-GP2 interface.

Funder

National Key Research and Development Program of China

Open Research Fund Program of the State Key Laboratory of Virology of China

Open Research Fund Program of CAS Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, and Open Research Fund Program of Wuhan National Bio-Safety Level 4 Lab of CAS

National Natural Science Foundation of China

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

Reference58 articles.

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2. The Curious Case of Arenavirus Entry, and Its Inhibition

3. Buchmeier MJ, de la Torre JC, Peters CJ. 2007. Fields virology, 4th ed. Lippincott-Raven, Philadelphia, PA.

4. Animal Models, Prophylaxis, and Therapeutics for Arenavirus Infections

5. Lassa fever

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