ST-193 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. IC50: 0.44 nM (Guanarito), 0.62 nM (Junin), 1.4 nM (Lassa) and 3.1 nM (Machupo)
ST-193 inhibits LASV pseudotypes with an IC50 of 1.6 nM.
ST-193 inhibits pseudotypes generated with other arenavirus envelopes as
well, including the remaining four commonly associated with hemorrhagic
fever (IC50s for Junín, Machupo, Guanarito, and Sabiá were
in the 0.2 to 12 nM range) but exhibits no antiviral activity against
pseudotypes incorporating either the GP from the LASV-related arenavirus
lymphocytic choriomeningitis virus or the unrelated G protein from
vesicular stomatitis virus, at concentrations of up to 10 μM.
ST-193 is found to be tolerated well when administered daily as an
intraperitoneal injection of either 25 or 100 mg/kg/day for 14 days.
ST-193-treated animals exhibit fewer signs of disease and enhance
survival when compared to the ribavirin or vehicle groups. Body
temperatures in all groups are elevated by day 9, but returned to normal
by day 19 postinfection in the majority of ST-193-treated animals. ST-193 treatment mediates a 2- to 3-log reduction in viremia relative to
vehicle-treated controls. The overall survival rate for the
ST-193-treated guinea pigs is 62.5% (10/16) compared with 0% in the
ribavirin (0/8) and vehicle (0/7) groups.
