The antiviral activity of licensed therapeutics against Mpox clade Ib, in vitro; alternative options for the treatment of Mpox

Clade Ib mpox is a newly emerged strain of the mpox virus (MPXV). The antiviral efficacy of 12 different therapeutic drugs was evaluated, in vitro using a live-virus, foci reduction assay, against MPXV clade Ib. We report that antiviral activity is retained against clade Ib with inhibitory concentrations (required to reduce the viral foci count by 50% (IC50)) of 0.025 {+/-} 0.018 and 43.8 {+/-} 15.2 M for tecovirimat and cidofovir, respectively. These values are not significantly different from those observed for clade IIb, when measured in the same foci reduction assay (IC50 values of 0.010 {+/-} 0.02 and 15.7 {+/-} 14.3 M for tecovirimat and cidofovir, respectively). Activity was also demonstrated for other antivirals, with the IC50 of the active metabolites of molnupiravir (EIDD-1931; 4.47 {+/-} 1.72 M) and remdesivir (GS-441524; 11.8 {+/-} 6.43 M) and with other licensed antivirals such as ribavirin (34.4 {+/-} 10.3 M) and baloxavir marboxil (22.6 {+/-} 10.5 M). In contrast, no inhibitory activity was observed with acyclovir, L-valacyclovir hydrochloride or favipiravir (IC50 >100 M). Interestingly, the anti-parasitic drugs nitazoxanide, mefloquine hydrochloride and chloroquine diphosphate, showed inhibitory activity against the clade Ib virus, with IC50 values of 14.5 {+/-} 3.41, 5.37 {+/-} 1.37 and 24.7 {+/-} 2.38 M, respectively. This study shows that several therapeutics, including several licensed antivirals, may offer alternative treatment options for mpox clade Ib.