Identification of a macrocyclic compound targeting the lassa virus polymerase
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Author/Creator ORCID
Date
2024-08-01
Type of Work
Department
Program
Citation of Original Publication
Aida-Ficken, Virginia, Jamie A. Kelly, Payel Chatterjee, M. Harley Jenks, Laura K. McMullan, César G.. Albarino, Joel M. Montgomery, Katherine L. Seley-Radtke, Christina F. Spiropoulou, and Mike Flint. "Identification of a Macrocyclic Compound Targeting the Lassa Virus Polymerase." Antiviral Research 228 (August 1, 2024): 105923. https://doi.org/10.1016/j.antiviral.2024.105923.
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This work was written as part of one of the author's official duties as an Employee of the United States Government and is therefore a work of the United States Government. In accordance with 17 U.S.C. 105, no copyright protection is available for such works under U.S. Law.
Public Domain
Public Domain
Abstract
There are no approved vaccines or therapeutics for Lassa virus (LASV) infections. To identify compounds with anti-LASV activity, we conducted a cell-based screening campaign at biosafety level 4 and tested almost 60,000 compounds for activity against an infectious reporter LASV. Hits from this screen included several structurally related macrocycles. The most potent, Mac128, had a sub-micromolar EC50 against the reporter virus, inhibited wild-type clade IV LASV, and reduced viral titers by 4 orders of magnitude. Mechanistic studies suggested that Mac128 inhibited viral replication at the level of the polymerase.