%0 Journal Article
%T Identification of a macrocyclic compound targeting the lassa virus polymerase.
%A Aida-Ficken V
%A Kelly JA
%A Chatterjee P
%A Jenks MH
%A McMullan LK
%A Albariño CG
%A Montgomery JM
%A Seley-Radtke KL
%A Spiropoulou CF
%A Flint M
%J Antiviral Res
%V 228
%N 0
%D 2024 Aug 4
%M 38844175
%F 10.103
%R 10.1016/j.antiviral.2024.105923
%X 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.