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Engineering Antiviral Agents via Surface Plasmon Resonance
Published on: June 14, 2022
SARS-CoV-2 resistance pathways to EDP-235
Kevin Wang1, Joyce Sweeney Gibbons2, Nalini Bisht2
1Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA.
Antiviral Research
|July 27, 2026
Summary
EDP-235, a novel COVID-19 therapeutic, shows a high barrier to SARS-CoV-2 resistance, outperforming nirmatrelvir. Understanding viral mutations is key for developing effective coronavirus treatments.
Area of Science:
- Virology
- Drug Discovery
- Molecular Biology
Background:
- Limited therapeutic options for SARS-CoV-2 infections necessitate new drug development.
- Understanding drug resistance mechanisms is crucial for effective antiviral therapies.
Purpose of the Study:
- To profile the resistance of EDP-235, a novel coronavirus 3CLpro inhibitor, against SARS-CoV-2.
- To compare the resistance barrier of EDP-235 with nirmatrelvir.
- To investigate resistance selection in an alphacoronavirus (HCoV-229E).
Main Methods:
- High-throughput passaging of SARS-CoV-2 under drug pressure.
- Sequencing to identify emergent mutations.
- Cellular reporter assays to determine resistance levels.
- Comparative resistance studies with nirmatrelvir and HCoV-229E.
Main Results:
- Multiple mutations conferring resistance to EDP-235 were identified, with L50F + E166A + P168S showing the highest resistance (578-fold).
- EDP-235 demonstrated a higher barrier to resistance compared to nirmatrelvir against SARS-CoV-2.
- Resistance mutations differed between SARS-CoV-2 and HCoV-229E, highlighting the impact of viral backbone.
Conclusions:
- EDP-235 exhibits a robust resistance profile, supporting its continued clinical development for COVID-19.
- The study provides insights into SARS-CoV-2 drug resistance mechanisms.
- Viral backbone influences resistance selection, emphasizing the need for virus-specific assessments.
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