{
  "abstract": "The SARS-CoV-2 main protease (Mpro) plays a crucial role in viral replication, making it an attractive target for antiviral drug development. This study evaluates the inhibitory potential of nineteen 6-substituted coumarin derivatives (1a-p and 2a-c) against Mpro using a FRET-based enzymatic assay. Among them, the chlorinated derivative 1f (AKE-9306) exhibited the highest potency with an IC₅₀ value of 61.77 µM. Enzyme kinetics analysis through Michaelis-Menten and Lineweaver-Burk plots revealed that compound 1f may act through a mixed-type inhibition mechanism with a preference for the free enzyme. In cellular assays, 1f showed significant antiviral efficacy (IC₅₀ = 16.02 µM, CC₅₀ >50 µM, selectivity index >3.12). Molecular docking and dynamics simulations confirmed its stable interaction within the Mpro active site, supported by MM-PBSA calculations. These findings identify compound 1f as a hit coumarin-based scaffold for further optimization toward improved SARS-CoV-2 Mpro inhibition and antiviral activity.",
  "abstract_shown": true,
  "affiliations": [
    "Biomedical Research Division, Korea Institute of Science and Technology (KIST) Seoul 02792 Republic of Korea ph_karem2000@mans.edu.eg gkeum@kist.re.kr.",
    "Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University Mansoura 35516 Egypt.",
    "Center for Natural Product Systems Biology, KIST Gangneung Institute of Natural Products Gangneung 25451 Republic of Korea dsong82@kist.re.kr.",
    "Natural Product Applied Science, KIST School, University of Science and Technology Gangneung 25451 Republic of Korea.",
    "Zoonotic Virus Laboratory, Institut Pasteur Korea Seongnam Republic of Korea seungtaek.kim@ip-korea.org.",
    "Department of Medicinal Chemistry, Faculty of Pharmacy, King Salman International University (KSIU) South Sinai 46612 Egypt.",
    "Department of Pharmaceutical Chemistry and Pharmacognosy, College of Pharmacy, Qassim University Buraydah 51452 Saudi Arabia.",
    "Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Kafrelsheikh University Kafrelsheikh P.O. Box 33516 Egypt wagdy2000@gmail.com.",
    "Division of Bio-Medical Science and Technology, KIST School, University of Science and Technology Seoul 02792 Republic of Korea."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Ashraf K El-Damasy",
      "orcid": "0000-0002-8446-0383"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Md Sofequl Islam Mukim",
      "orcid": "0009-0005-4806-0111"
    },
    {
      "affs": [
        4
      ],
      "name": "Sangeun Jeon"
    },
    {
      "affs": [
        5
      ],
      "name": "Mahmoud A El Hassab"
    },
    {
      "affs": [
        6
      ],
      "name": "Suliman A Almahmoud"
    },
    {
      "affs": [
        0
      ],
      "name": "Eun-Kyoung Bang"
    },
    {
      "affs": [
        7
      ],
      "name": "Wagdy M Eldehna",
      "orcid": "0000-0001-6996-4017"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Dae-Geun Song"
    },
    {
      "affs": [
        4
      ],
      "name": "Seungtaek Kim"
    },
    {
      "affs": [
        0,
        8
      ],
      "name": "Gyochang Keum"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/bjcmhgn8ve09r.bib",
  "cited_by": 0,
  "doi": "10.1039/d6ra07298d",
  "fulltext_url": "https://europepmc.org/articles/PMC13637745",
  "id": "bjcmhgn8ve09r",
  "issns": [
    "2046-2069"
  ],
  "landing_url": "https://europepmc.org/article/MED/42835829",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2725|SARS-CoV-2 and COVID-19 Research"
    ]
  ],
  "openalex": "W7220404958",
  "pdf_url": "https://europepmc.org/articles/PMC13637745?pdf=render",
  "pmcid": "PMC13637745",
  "pmid": "42835829",
  "published": "2026-10-05",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/bjcmhgn8ve09r.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:10Z",
      "native_id": "MED:42835829",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42835829"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2725|SARS-CoV-2 and COVID-19 Research",
      "subfield": "infectious-disease"
    }
  ],
  "title": "Evaluation of 6-substituted coumarins as SARS-CoV-2 main protease inhibitors: enzymatic, cellular, and computational insights.",
  "title_text": "Evaluation of 6-substituted coumarins as SARS-CoV-2 main protease inhibitors: enzymatic, cellular, and computational insights.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:18:10Z",
  "url": "https://research.draconitic.com/paper/bjcmhgn8ve09r",
  "venue": "RSC advances",
  "versions": []
}