{Reference Type}: Journal Article
{Title}: Identification of a macrocyclic compound targeting the lassa virus polymerase.
{Author}: Aida-Ficken V;Kelly JA;Chatterjee P;Jenks MH;McMullan LK;Albariño CG;Montgomery JM;Seley-Radtke KL;Spiropoulou CF;Flint M;
{Journal}: Antiviral Res
{Volume}: 228
{Issue}: 0
{Year}: 2024 Aug 4
{Factor}: 10.103
{DOI}: 10.1016/j.antiviral.2024.105923
{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.