Key result
Novel synergistic combinations of rupintrivir-vemurafenib, vemurafenib-pleconaril, and rupintrivir-pleconaril successfully inhibited echovirus 1 replication in vitro.
Why the study?
Enterovirus infections cause illnesses ranging from mild fevers to potentially fatal conditions, but there are no approved treatments.
Combinations of rupintrivir, vemurafenib, and pleconaril show synergistic anti-enteroviral activity in vitro, suggesting potential for lower-dose, lower-toxicity clinical applications.
Background: Enterovirus infections affect people around the world, causing a range of illnesses, from mild fevers to severe, potentially fatal conditions. There are no approved treatments for enterovirus infections. Methods: We have tested our library of broad-spectrum antiviral agents (BSAs) against echovirus 1 (EV1) in human adenocarcinoma alveolar basal epithelial A549 cells. We also tested combinations of the most active compounds against EV1 in A549 and human immortalized retinal pigment epithelium RPE cells. Results: We confirmed anti-enteroviral activities of pleconaril, rupintrivir, cycloheximide, vemurafenib, remdesivir, emetine, and anisomycin and identified novel synergistic rupintrivir–vemurafenib, vemurafenib–pleconaril and rupintrivir–pleconaril combinations against EV1 infection. Conclusions: Because rupintrivir, vemurafenib, and pleconaril require lower concentrations to inhibit enterovirus replication in vitro when combined, their cocktails may have fewer side effects in vivo and, therefore, should be further explored in preclinical and clinical trials against EV1 and other enterovirus infections.
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Žusinaite et al. (2022) studied Enterovirus infection (echovirus 1). Broad-spectrum antiviral agents and combinations (rupintrivir, vemurafenib, pleconaril) was evaluated on Anti-enteroviral activity and synergistic effects against EV1 infection. Novel synergistic combinations of rupintrivir-vemurafenib, vemurafenib-pleconaril, and rupintrivir-pleconaril successfully inhibited echovirus 1 replication in vitro.
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