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.
