{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T12:23:05Z","timestamp":1792498985941,"version":"4.5.0"},"reference-count":71,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T00:00:00Z","timestamp":1741737600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Dr. B.R. Ambedkar Center for Biomedical Research, University of Delhi","award":["IoE\/2021\/12\/FRP"],"award-info":[{"award-number":["IoE\/2021\/12\/FRP"]}]},{"name":"The Institution of Eminence","award":["IoE\/2021\/12\/FRP"],"award-info":[{"award-number":["IoE\/2021\/12\/FRP"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>The main protease (Mpro or 3CLpro or nsp5) of SARS-CoV-2 is crucial to the life cycle and pathogenesis of SARS-CoV-2, making it an attractive drug target to develop antivirals. This study employed the virtual screening of a few phytochemicals, and the resultant best compound, Scopoletin, was further investigated by a FRET-based enzymatic assay, revealing an experimental IC50 of 15.75 \u00b5M. The impact of Scopoletin on Mpro was further investigated by biophysical and MD simulation studies. Fluorescence spectroscopy identified a strong binding constant of 3.17 \u00d7 104 M\u207b1 for Scopoletin binding to Mpro, as demonstrated by its effective fluorescence quenching of Mpro. Additionally, CD spectroscopy showed a significant reduction in the helical content of Mpro upon interaction with Scopoletin. The findings of thermodynamic measurements using isothermal titration calorimetry (ITC) supported the spectroscopic data, indicating a tight binding of Scopoletin to Mpro with a KA of 2.36 \u00d7 103 M\u22121. Similarly, interaction studies have also revealed that Scopoletin forms hydrogen bonds with the amino acids nearest to the active site, and this has been further supported by molecular dynamics simulation studies. These findings indicate that Scopoletin may be developed as a potential antiviral treatment for SARS-CoV-2 by targeting Mpro.<\/jats:p>","DOI":"10.3390\/v17030402","type":"journal-article","created":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T07:31:42Z","timestamp":1741764702000},"page":"402","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Biochemical Screening of Phytochemicals and Identification of Scopoletin as a Potential Inhibitor of SARS-CoV-2 Mpro, Revealing Its Biophysical Impact on Structural Stability"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6990-9528","authenticated-orcid":false,"given":"Sarika","family":"Bano","sequence":"first","affiliation":[{"name":"Laboratory for Proteins and Structural Biology, Dr. B.R. 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