Key result
Remdesivir shows high in vitro potency against RSVA and hPIV3, with dual combinations producing marked synergy.
Why the study?
Despite the major global health burden of respiratory viruses, effective broad-spectrum antiviral therapeutic options remain limited.
RdRp inhibitor combinations demonstrate synergistic antiviral activity against RSVA and hPIV3 in primary human airway culture models, highlighting their potential for broad-spectrum antiviral regimens.
Answers are grounded in this paper and cite their sources.
In vitro RdRp inhibitor data against RSVA/hPIV3 are hypothesis-generating; clinical efficacy remains untested and should not alter practice.
Despite the huge global health burden presented by respiratory viruses, effective broad-spectrum antiviral therapeutic options remain limited. Here we evaluated the antiviral activity of four RNA-dependent RNA polymerase (RdRp) inhibitors, remdesivir, ribavirin, favipiravir, and molnupiravir, as monotherapy or dual-drug combinations against respiratory syncytial virus (subtype A, RSVA) and human parainfluenza (serotype 3, hPIV3) using epithelial cell lines and primary human airway culture models. Remdesivir showed the greatest potency across both viruses, while ribavirin and favipiravir also demonstrated inhibition. Molnupiravir was active against RSVA but not hPIV3. Several dual-drug combinations, including remdesivir–favipiravir, remdesivir–molnupiravir and favipiravir–molnupiravir, produced marked synergy against RSVA, and more limited synergy for hPIV3. Antiviral efficacy was validated in primary airway epithelial cultures, where effective concentrations preserved epithelial integrity and attenuated viral disruption of ciliary function. Across both viruses, increasing antiviral exposure was associated with dose-dependent signature mutagenesis. Antivirals induced significantly higher RSVA mutation burden in the primary airway model. These findings highlight the therapeutic potential of RdRp inhibitor combinations for RSVA and hPIV3, provide mechanistic insight through antiviral-related mutational signatures, and demonstrate advantages of the primary human airway culture model for development of effective multi-drug regimens and broad-spectrum antiviral preparedness.
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Ellis et al. (2026) studied RSVA and hPIV3 infection. RdRp inhibitors (remdesivir, ribavirin, favipiravir, molnupiravir) vs. Untreated controls was evaluated on Viral inhibition (EC50). Remdesivir demonstrated the highest potency against RSVA (EC50 3.6 mg/L) and hPIV3 (EC50 1.1 mg/L), and dual-drug combinations produced marked synergy against RSVA in epithelial cell models.
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