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  • 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; 2024 Aug; 228():105923. PubMed ID: 38844175.
    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.
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