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China","award":["2021B1212030011"],"award-info":[{"award-number":["2021B1212030011"]}]},{"name":"Science and Technology Plan Project of Guangdong Province of China","award":["2023YFC2307800"],"award-info":[{"award-number":["2023YFC2307800"]}]},{"name":"Science and Technology Plan Project of Guangdong Province of China","award":["2023AB08097"],"award-info":[{"award-number":["2023AB08097"]}]},{"name":"Science and Technology Plan Project of Guangdong Province of China","award":["RAZ24010001"],"award-info":[{"award-number":["RAZ24010001"]}]},{"name":"Science and Technology Plan Project of Guangdong Province of China","award":["32161160303"],"award-info":[{"award-number":["32161160303"]}]},{"name":"Science and Technology Plan Project of Guangdong Province of China","award":["JCYJ20230807090212024"],"award-info":[{"award-number":["JCYJ20230807090212024"]}]},{"name":"Science and Technology Plan Project of Guangdong Province of China","award":["2021B1212030011"],"award-info":[{"award-number":["2021B1212030011"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Enterovirus 71 (EV71), a typical representative of unenveloped RNA viruses, is the main pathogenic factor responsible for hand, foot, and mouth disease (HFMD) in infants. This disease seriously threatens the health and lives of humans worldwide, especially in the Asia\u2013Pacific region. Numerous animal antimicrobial peptides have been found with protective functions against viruses, bacteria, fungi, parasites, and other pathogens, but there are few studies on the use of scorpion-derived antimicrobial peptides against unenveloped viruses. Here, we investigated the antiviral activities of scorpion venom antimicrobial peptide BmKn2 and five derivatives, finding that BmKn2 and its derivative BmKn2-T5 exhibit a significant inhibitory effect on EV71. Although both peptides exhibit characteristics typical of amphiphilic \u03b1-helices in terms of their secondary structure, BmKn2-T5 displayed lower cellular cytotoxicity than BmKn2. BmKn2-T5 was further found to inhibit EV71 in a dose-dependent manner in vitro. Moreover, time-of-drug-addition experiments showed that BmKn2-T5 mainly restricts EV71, but not its virion or replication, at the early stages of the viral cycle. Interestingly, BmKn2-T5 was also found to suppress the replication of the enveloped viruses DENV, ZIKV, and HSV-1 in the early stages of the viral cycle, which suggests they may share a common early infection step with EV71. Together, the results of our study identified that the scorpion-derived antimicrobial peptide BmKn2-T5 showed valuable antiviral properties against EV71 in vitro, but also against other enveloped viruses, making it a potential new candidate therapeutic molecule.<\/jats:p>","DOI":"10.3390\/biom14050545","type":"journal-article","created":{"date-parts":[[2024,5,1]],"date-time":"2024-05-01T10:33:31Z","timestamp":1714559611000},"page":"545","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Scorpion Venom Antimicrobial Peptide Derivative BmKn2-T5 Inhibits Enterovirus 71 in the Early Stages of the Viral Life Cycle In Vitro"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-3379-9022","authenticated-orcid":false,"given":"Zhiqiang","family":"Xia","sequence":"first","affiliation":[{"name":"Center for Evolution and Conservation Biology, Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou), Guangzhou 511458, China"},{"name":"State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China"},{"name":"School of Biological and Food Processing Engineering, Huanghuai University, Zhumadian 463000, China"},{"name":"Shenzhen Research Institute, Wuhan University, Shenzhen 518057, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huijuan","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weilie","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Infectious Diseases, Guangzhou Eighth People\u2019s Hospital, Guangzhou Medical University, Guangzhou 510060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8124-9697","authenticated-orcid":false,"given":"Aili","family":"Wang","sequence":"additional","affiliation":[{"name":"Center for Evolution and Conservation Biology, Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou), Guangzhou 511458, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhijian","family":"Cao","sequence":"additional","affiliation":[{"name":"Center for Evolution and Conservation Biology, Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou), Guangzhou 511458, China"},{"name":"State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China"},{"name":"Shenzhen Research Institute, Wuhan University, Shenzhen 518057, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1186\/s43088-022-00258-4","article-title":"Global emergence of Enterovirus 71: A systematic review","volume":"11","author":"Nayak","year":"2022","journal-title":"Beni Suef Univ. J. Basic Appl. Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1274","DOI":"10.1126\/science.1218713","article-title":"Crystal structure of human enterovirus 71","volume":"336","author":"Plevka","year":"2012","journal-title":"Science"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"785","DOI":"10.3390\/v15030785","article-title":"EV-A71 mechanism of entry: Receptors\/co-receptors, related pathways and inhibitors","volume":"15","author":"Hu","year":"2023","journal-title":"Viruses"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e2322","DOI":"10.1002\/rmv.2322","article-title":"Does enterovirus 71 urge for effective vaccine control strategies? Challenges and current opinion","volume":"32","author":"Swain","year":"2022","journal-title":"Rev. Med. Virol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1001\/jama.291.2.222","article-title":"Transmission and clinical features of enterovirus 71 infections in household contacts in Taiwan","volume":"291","author":"Chang","year":"2004","journal-title":"JAMA"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1080\/14787210.2021.1851194","article-title":"Recent advances in the understanding of enterovirus A71 infection: A focus on neuropathogenesis","volume":"19","author":"Tee","year":"2021","journal-title":"Expert Rev. Anti Infect. Ther."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1016\/S1473-3099(13)70342-6","article-title":"Hand, foot, and mouth disease in China, 2008-12: An epidemiological study","volume":"14","author":"Xing","year":"2014","journal-title":"Lancet Infect. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"191","DOI":"10.7883\/yoken1952.34.191","article-title":"A large-scale epidemic of hand, foot and mouth disease associated with enterovirus 71 infection in Japan in 1978","volume":"34","author":"Tagaya","year":"1981","journal-title":"Jpn. J. Med. Sci. Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1017\/S0950268815002137","article-title":"Basic reproduction number of coxsackievirus type A6 and A16 and enterovirus 71: Estimates from outbreaks of hand, foot and mouth disease in Singapore, a tropical city-state","volume":"144","author":"Lim","year":"2016","journal-title":"Epidemiol. Infect."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1186\/s12929-019-0573-2","article-title":"The history of enterovirus A71 outbreaks and molecular epidemiology in the Asia-Pacific region","volume":"26","author":"Puenpa","year":"2019","journal-title":"J. Biomed. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"199336","DOI":"10.1016\/j.virusres.2024.199336","article-title":"Inhibition of EV71 replication by an interferon-stimulated gene product L3HYPDH","volume":"342","author":"Liu","year":"2024","journal-title":"Virus Res."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Liu, H., Xue, Q., Yang, F., Cao, W., Liu, P., Liu, X., Zhu, Z., and Zheng, H. (2024). Foot-and-mouth disease virus VP1 degrades YTHDF2 through autophagy to regulate IRF3 activity for viral replication. Autophagy, 1\u201319.","DOI":"10.1080\/15548627.2024.2330105"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Fan, T., Liu, B., Yao, H., Chen, X., Yang, H., Guo, S., Wu, B., Li, X., Li, X., and Xun, M. (2024). Cathelicidin peptide analogues inhibit EV71 infection through blocking viral entry and uncoating. 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Microbes Infect."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/14\/5\/545\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:38:21Z","timestamp":1760107101000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/14\/5\/545"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,1]]},"references-count":50,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2024,5]]}},"alternative-id":["biom14050545"],"URL":"https:\/\/doi.org\/10.3390\/biom14050545","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,1]]}}}