Publication date: Jun 19, 2026
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused significant global loss and social disruption. Although large-scale vaccination campaigns and naturally acquired immunity have reduced viral transmission, the rapid evolution of the viral genome-driven by the lack of proofreading during replication-continues to pose a major public health threat. The current SARS-CoV-2 main protease inhibitor (Mpro), Paxlovid, substantially lowers hospitalization rates but is associated with adverse effects and drug-drug interactions with many medications. To discover more effective and safer treatments, we conducted a large-scale virtual screening to identify novel structural scaffolds targeting viral Mpro. This effort yielded a series of spiropyrrolidinoxindole derivative hits with promising low-micromolar inhibitory activity. Through preliminary analysis of the structure-activity relationship and proposed binding conformations, our findings provide a basis for rational structural optimization and may facilitate the development of potent, safer spiropyrrolidinoxindole-based therapeutics against severe COVID-19.
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Semantics
| Type | Source | Name |
|---|---|---|
| disease | MESH | Coronavirus disease 2019 |
| disease | MESH | severe acute respiratory syndrome |