{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T04:10:39Z","timestamp":1790050239207,"version":"4.0.1"},"reference-count":116,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,10,14]],"date-time":"2021-10-14T00:00:00Z","timestamp":1634169600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Health","award":["PO1 AI 057788"],"award-info":[{"award-number":["PO1 AI 057788"]}]},{"DOI":"10.13039\/100000928","name":"Welch Foundation","doi-asserted-by":"publisher","award":["Q1279"],"award-info":[{"award-number":["Q1279"]}],"id":[{"id":"10.13039\/100000928","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Human norovirus (HuNoV) infection is a global health and economic burden. Currently, there are no licensed HuNoV vaccines or antiviral drugs available. The protease encoded by the HuNoV genome plays a critical role in virus replication by cleaving the polyprotein and is an excellent target for developing small-molecule inhibitors. The current strategy for developing HuNoV protease inhibitors is by targeting the enzyme\u2019s active site and designing inhibitors that bind to the substrate-binding pockets located near the active site. However, subtle differential conformational flexibility in response to the different substrates in the polyprotein and structural differences in the active site and substrate-binding pockets across different genogroups, hamper the development of effective broad-spectrum inhibitors. A comparative analysis of the available HuNoV protease structures may provide valuable insight for identifying novel strategies for the design and development of such inhibitors. The goal of this review is to provide such analysis together with an overview of the current status of the design and development of HuNoV protease inhibitors.<\/jats:p>","DOI":"10.3390\/v13102069","type":"journal-article","created":{"date-parts":[[2021,10,14]],"date-time":"2021-10-14T23:02:16Z","timestamp":1634252536000},"page":"2069","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Norovirus Protease Structure and Antivirals Development"],"prefix":"10.3390","volume":"13","author":[{"given":"Boyang","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8340-8911","authenticated-orcid":false,"given":"Liya","family":"Hu","sequence":"additional","affiliation":[{"name":"Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongcheng","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Chemical Biology, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ketki","family":"Patil","sequence":"additional","affiliation":[{"name":"Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5631-8534","authenticated-orcid":false,"given":"Sasirekha","family":"Ramani","sequence":"additional","affiliation":[{"name":"Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert L.","family":"Atmar","sequence":"additional","affiliation":[{"name":"Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA"},{"name":"Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary K.","family":"Estes","sequence":"additional","affiliation":[{"name":"Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA"},{"name":"Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1172-2071","authenticated-orcid":false,"given":"B. 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