Remdesivir and Favipiravir as potential antivirals for poliovirus: In vitro efficacy and RNA-dependent RNA polymerase...

Complete poliovirus eradication requires managing chronic excreters and controlling potential outbreaks. RNA-dependent RNA Polymerase (RdRp) inhibitors represent promising candidates for this purpose. The antiviral activities of Remdesivir, Favipiravir, and Ribavirin against Sabin-like poliovirus types 1 (SL1) and 3 (SL3) were evaluated in HeLa cells individually and in combination. Antiviral effects were measured by cytopathic effect inhibition, MTT assay, and qRT-PCR. Drug-drug interactions were analyzed using Synergy Finder Plus. Molecular docking was performed to evaluate RdRp binding affinity. Remdesivir demonstrated the modest activity with low EC₅₀ values of 47 μM (SL1) and 27 μM (SL3), while Favipiravir also showed suppression of replication at higher concentrations. Ribavirin was ineffective against SL3 and only partially inhibited SL1 at a concentration of 3500 μM. Combination treatments, especially those involving Remdesivir and Favipiravir, exhibited antagonism due to their overlapping targeting of the RdRp active site. While triple-drug treatment improved the inhibition of SL1, no additional benefit was observed against SL3. Docking analysis confirmed that Remdesivir-TP had the highest RdRp binding affinity with a ΔG value of -8.1 kcal/mol, followed by Ribavirin with -7.6 kcal/mol and Favipiravir-TP with -7.5 kcal/mol. Remdesivir and Favipiravir demonstrated notable antiviral effects against poliovirus in vitro, whereas Ribavirin showed less efficacy. Nevertheless, combining nucleoside analogues resulted in antagonistic effects, highlighting the importance of careful consideration when designing combination therapies. These results encourage continued investigation of Remdesivir and Favipiravir as potential antiviral agents for poliovirus, emphasizing the importance of selecting drugs based on their mechanisms of action in combination approaches.