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

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Abstract 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% (IC 50 )) of 0.025 ± 0.018 and 43.8 ± 15.2 μM 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 (IC 50 values of 0.010 ± 0.02 and 15.7 ± 14.3 μM for tecovirimat and cidofovir, respectively). Activity was also demonstrated for other antivirals, with the IC 50 of the active metabolites of molnupiravir (EIDD-1931; 4.47 ± 1.72 μM) and remdesivir (GS-441524; 11.8 ± 6.43 μM) and with other licensed antivirals such as ribavirin (34.4 ± 10.3 μM) and baloxavir marboxil (22.6 ± 10.5 μM). In contrast, no inhibitory activity was observed with acyclovir, L-valacyclovir hydrochloride or favipiravir (IC 50 >100 μM). Interestingly, the anti-parasitic drugs nitazoxanide, mefloquine hydrochloride and chloroquine diphosphate, showed inhibitory activity against the clade Ib virus, with IC 50 values of 14.5 ± 3.41, 5.37 ± 1.37 and 24.7 ± 2.38 μM, respectively. This study shows that several therapeutics, including several licensed antivirals, may offer alternative treatment options for mpox clade Ib.

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