# Antiviral Activity of Remdesivir and Obeldesivir Against SARS-CoV-2 Omicron Subvariants That Were Circulating from September 2023 Through June 2025

## TL;DR

This study shows that remdesivir and obeldesivir remain effective against new SARS-CoV-2 Omicron subvariants circulating from September 2023 to June 2025.

## Contribution

The study confirms the continued antiviral efficacy of remdesivir and obeldesivir against newly emerging Omicron subvariants.

## Key findings

- Remdesivir and obeldesivir retained activity against Omicron subvariants BA.2.86.1, JN.1.7, KP.2, and others.
- Only one new Nsp12 substitution (D284Y) was observed in NB.1.8.1, which did not confer resistance to either drug.
- Both drugs remain effective against SARS-CoV-2 variants, supporting their clinical use.

## Abstract

With the ongoing emergence of SARS-CoV-2 variants, continued surveillance of antiviral susceptibility remains critical for detecting resistance that could compromise treatment efficacy. This study evaluated the activity of 2 SARS-CoV-2 RNA-dependent RNA polymerase (Nsp12) inhibitors against emerging Omicron variants: remdesivir (RDV), an approved antiviral for the treatment of COVID-19, and obeldesivir (ODV), an oral prodrug that shares the same parent nucleoside as RDV. Both RDV and ODV were shown to retain antiviral activity against the Omicron subvariants BA.2.86.1, JN.1.7, KP.2, KP.3.1.1, KP.3.3, LP.8.1, NB.1.8.1, XBB.2, XEC, and XFG compared with wild-type reference strains. Only 1 new lineage-defining Nsp12 substitution, D284Y (detected in NB.1.8.1), was observed. Phenotypic analysis demonstrated that a replicon containing this substitution remained susceptible to both RDV and ODV. These findings are consistent with previous studies showing that RDV and ODV retain potent activity against previously identified Omicron variants, support the continued clinical use of RDV against circulating SARS-CoV-2 variants, and reinforce the potential of ODV as an oral antiviral therapeutic.