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May 31, 2026npj Antimicrobials and ResistanceOpen Access

Remdesivir shows high in vitro potency against RSVA and hPIV3, with dual combinations producing marked synergy.

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Why the study?

Despite the major global health burden of respiratory viruses, effective broad-spectrum antiviral therapeutic options remain limited.

Population

Epithelial cell lines and primary human airway culture models infected with RSVA and hPIV3

Comparison

RdRp inhibitors (remdesivir, ribavirin, favipiravir, molnupiravir) as monotherapy vs dual-drug combinations

Design

Preclinical in vitro and primary culture study

Key result

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.

Authors

SESamuel EllisGreat Ormond Street HospitalAJAmy JacobsUniversity College LondonSZShengyuan ZhangGreat Ormond Street Hospital

Discussion

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Overview

In vitro RdRp inhibitor data against RSVA/hPIV3 are hypothesis-generating; clinical efficacy remains untested and should not alter practice.

Key Points

  • This research aims to evaluate the antiviral effectiveness of polymerase inhibitors against RSVA and hPIV3 in epithelial cell models.
  • Assessed four RdRp inhibitors as monotherapy and in dual-drug combinations.
  • Utilized epithelial cell lines and primary human airway cultures for antiviral efficacy.
  • Measured viral disruption of ciliary function and monitored mutational signatures.
  • Remdesivir displayed the highest antiviral potency against both viruses.
  • Combination therapies showed marked synergy for RSVA, with effective concentrations preserving epithelial integrity.
  • Higher antiviral exposure correlated with increased RSVA mutation burden in primary airway cultures.

Structured PICO

P
Population
Epithelial cell lines and primary human airway culture models infected with respiratory syncytial virus (subtype A, RSVA) and human parainfluenza (serotype 3, hPIV3)
I
Intervention
RNA-dependent RNA polymerase (RdRp) inhibitors (remdesivir, ribavirin, favipiravir, and molnupiravir) as monotherapy or dual-drug combinations
O
Outcome
Antiviral activity (inhibition), preservation of epithelial integrity, attenuation of viral disruption of ciliary function, and mutational signaturessurrogate

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.

Limitations

  • In vitro study design
  • Cell line models incompletely represent the complexity of the human airway epithelium
  • Cytotoxicity at higher doses for some drugs confounded viral inhibition measurements

Cite This Study

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.

synapsesocial.com/papers/6a1bd1b05783ba022b6fd333https://doi.org/10.1038/s44259-026-00222-7
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