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.
摘要：
目前还没有批准的用于拉沙病毒(LASV)感染的疫苗或治疗剂。为了鉴定具有抗LASV活性的化合物，我们在生物安全4级下进行了基于细胞的筛查活动,并测试了近6万种化合物对感染性报道分子LASV的活性.来自该筛选的命中包括几个结构相关的大环。最有力的,Mac128对报告病毒具有亚微摩尔EC50，抑制野生型进化枝IVLASV，并将病毒滴度降低4个数量级。机制研究表明，Mac128在聚合酶水平上抑制病毒复制。
