Key result
Once-daily oral obeldesivir at 30 or 90 mg/kg significantly reduced RSV viral RNA area under the curve by 69-92% in the upper and lower respiratory tracts of infected African green monkeys.
Why the study?
Respiratory syncytial virus causes significant morbidity and mortality in high-risk populations, but effective oral therapeutics are lacking despite available prophylactics.
Does obeldesivir reduce viral RNA levels in an African green monkey RSV infection model?
Does obeldesivir reduce viral RNA levels in an African green monkey RSV infection model?
Oral obeldesivir demonstrates potent antiviral activity against RSV clinical isolates and significantly reduces viral replication in a non-human primate model, supporting its clinical evaluation.
Answers are grounded in this paper and cite their sources.
Supports clinical evaluation of oral obeldesivir for RSV; leaves open translation from primate models to patients.
Respiratory syncytial virus (RSV) is a significant cause of morbidity and mortality in high-risk populations. Although prophylactic options are available, there are no effective oral therapeutics for RSV infection. Obeldesivir (ODV) is an orally bioavailable prodrug of the nucleoside analog GS-441524, which is converted intracellularly to its active nucleoside triphosphate and inhibits the RSV RNA polymerase. Here we report the potent antiviral activity of ODV against geographically and temporally diverse RSV A and B clinical isolates (EC 50 : 0.20-0.66 μM). Resistance selection studies with ODV and GS-441524 against RSV identified a single amino acid substitution, I777L, in the L polymerase with reduced susceptibility (3.3-3.8-fold) to ODV and GS-441524, indicating a high barrier for resistance development. In an African green monkey RSV infection model, once-daily oral ODV doses of 30 or 90 mg/kg initiated ∼24 hours post-infection significantly reduced log 10 viral RNA copies/mL×day area under the curve by 69-92% in the upper and lower respiratory tracts. Together, these preclinical data support the clinical evaluation of ODV for the treatment of RSV infection.
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Pitts et al. (2025) studied Respiratory Syncytial Virus (RSV) infection (n=15). Obeldesivir vs. Vehicle was evaluated on Mean 15-day log10 RSV RNA area under the curve (AUC) in the upper and lower respiratory tracts (69-92% reduction, p=<0.05). Once-daily oral obeldesivir at 30 or 90 mg/kg significantly reduced RSV viral RNA area under the curve by 69-92% in the upper and lower respiratory tracts of infected African green monkeys.
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