A novel small-molecule arenaviruse inhibitor that exhibits strong anti-LCMV activity (IC50<1 uM) without cell toxicity.

ST-193 hydrochloride is a potent broad-spectrum arenavirus inhibitor; inhibits Guanarito, Junin, Lassa and Machupo virus with IC50 values of 0.44, 0.62, 1.4 and 3.1 nM, respectively.

ARN-75039 (ARN75039) is a potent, small molecule fusion inhibitor of arenavirus, inhibits pseudotyped entry of pGTOV and pCHAPV with EC50 of 0.13 and 4.3 nM, respectively.ARN-75039 demonstrated sub-nanomolar EC50 activity against pTCRV that further translated to native wild-and NWAs, including LASV, JUNV and MACV, in pseudotyped virus assays and against native replicative LASV and JUNV.ARN-75039 also potently inhibits mutant T434I pTCRV variant with EC50 of 29 nM.ARN-75039 dramatically improved survival outcome and potently inhibited TCRV replication in serum and various tissues at doses of 10 and 35 mg/kg, provided highly significant post-exposure protection in mice against TCRV infection.

ARN-75041 (ARN75041) is a potent, small molecule fusion inhibitor of arenavirus, inhibits pseudotyped entry of pGTOV and pCHAPV with EC50 of 1.7 and 15.3 nM, respectively. ARN-75041 demonstrated sub-nanomolar against native replicative LASV (LASV EC90<0.3 nM) and JUNV (EC90=6.2 nM).ARN-75041 also potently inhibits mutant T434I pTCRV variant with EC50 of 29 nM.ARN-75041 dramatically improved survival outcome and potently inhibited TCRV replication in serum and various tissues at doses of 10 and 35 mg/kg, provided highly significant post-exposure protection in mice against TCRV infection.