{
  "abstract": "The main protease (Mpro) is a prime target for anti-SARS-CoV-2 drugs. Herein, we describe the structure-based covalent modifications that generate new nonpeptidic covalent Mpro inhibitors. The compounds exhibit strong inhibition against Mpro at submicromolar levels. The deuterated lead compound exhibits submicromolar antiviral activity against wild-type SARS-CoV-2 and Omicron variants. Biolayer interferometry analysis indicates a strong binding affinity for Mpro. The mass spectrometry results confirm the covalent bonding of the compound with the cysteine residue of Mpro. Taken together, the data may support the deuterated compound as a new lead for developing anti-SARS-CoV-2 drugs and further reveal the feasibility of using chloroacetyl for structure-based covalent drug design.",
  "abstract_shown": true,
  "affiliations": [
    "Dr. Neher's Biophysics Laboratory for Innovative Drug Discovery, State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macao 999078, China.",
    "State Key Laboratory of Antiviral Drugs, Pingyuan Laboratory, School of Pharmaceutical Sciences, Henan Normal University, Xinxiang 453007, China.",
    "Centre for Artificial Intelligence Driven Drug Discovery, Faculty of Applied Sciences, Macao Polytechnic University, Macao 999078, China.",
    "State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510000, China.",
    "College of Chemistry, State Key Laboratory of Antiviral Drugs, Pingyuan Laboratory, Zhengzhou University, Zhengzhou 450001, China."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Honglei Bao"
    },
    {
      "affs": [
        1
      ],
      "name": "Lingchen Sun"
    },
    {
      "affs": [
        0
      ],
      "name": "Shilin Gong",
      "orcid": "0000-0001-7707-417X"
    },
    {
      "affs": [
        2
      ],
      "name": "Li Qin"
    },
    {
      "affs": [
        1
      ],
      "name": "Jiawei Xu"
    },
    {
      "affs": [
        0
      ],
      "name": "Jianlin Wu",
      "orcid": "0000-0002-3875-185X"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Chunhua Ma",
      "orcid": "0000-0001-7613-6471"
    },
    {
      "affs": [
        3
      ],
      "name": "Qinhai Ma"
    },
    {
      "affs": [
        2
      ],
      "name": "Xiaojun Yao",
      "orcid": "0000-0001-9958-8438"
    },
    {
      "affs": [
        4
      ],
      "name": "Bin Yu",
      "orcid": "0000-0002-7207-643X"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/4zc1vr27vjbw2.bib",
  "cited_by": 0,
  "doi": "10.1021/acsbiomedchemau.6c00072",
  "fulltext_url": "https://europepmc.org/articles/PMC13692733",
  "id": "4zc1vr27vjbw2",
  "issns": [
    "2694-2437"
  ],
  "landing_url": "https://europepmc.org/article/MED/42921030",
  "language": "eng",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2725|SARS-CoV-2 and COVID-19 Research"
    ]
  ],
  "openalex": "W7172439055",
  "pdf_url": "https://europepmc.org/articles/PMC13692733?pdf=render",
  "pmcid": "PMC13692733",
  "pmid": "42921030",
  "published": "2026-07-27",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/4zc1vr27vjbw2.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:21:02Z",
      "native_id": "MED:42921030",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42921030"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2725|SARS-CoV-2 and COVID-19 Research",
      "subfield": "infectious-disease"
    }
  ],
  "title": "Structure-Based Design of New Nonpeptidic Covalent Mpro Inhibitors against SARS-CoV‑2 and Omicron Variants.",
  "title_text": "Structure-Based Design of New Nonpeptidic Covalent Mpro Inhibitors against SARS-CoV‑2 and Omicron Variants.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:21:02Z",
  "url": "https://research.draconitic.com/paper/4zc1vr27vjbw2",
  "venue": "ACS bio & med chem Au",
  "versions": []
}