Moringin as a Lead Compound for Anti‐Enteroviruses and Coronaviruses Broad‐Spectrum Inhibition of Viral Proteases: Comparative Evaluation With Glucomoringin and Antiviral Agents

Enteroviruses (EVs) and Coronaviruses (CoVs) are single‐stranded RNA viruses known for their high pathogenicity and significant threat to public health worldwide. These viruses cause widespread respiratory illnesses in humans, resulting in considerable rates of sickness and death, which strain medical resources and healthcare systems. Beyond human health, their capacity to infect livestock leads to economic damages that affect food supply and the livelihoods of farming communities. Viral proteases, EV 3C protease (3C pro ) and CoV 3C‐like protease (3CL pro ) are essential for viral polyprotein processing and replication, making them key antiviral targets. We show that moringin, isothiocyanate derived from Moringa oleifera , broadly inhibits both 3C pro and 3CL pro activities in fluorescence assays. LC‐MS/MS and structural modeling reveal hydrogen‐bond interactions of moringin within their catalytic sites, reducing enzymatic activity. Biolayer interferometry confirms higher binding affinity to active versus inactive proteases. Plaque reduction assays demonstrate moringin's efficacy in suppressing EV and CoV replication in cells. These results highlight moringin's potential as a broad‐spectrum antiviral agent targeting conserved viral proteases.