Identification of a macrocyclic compound targeting the lassa virus polymerase.

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.

SUBMITTER: Aida-Ficken V 

PROVIDER: S-EPMC11995929 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature