{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T17:58:21Z","timestamp":1771955901349,"version":"3.50.1"},"reference-count":47,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2024,8,16]],"date-time":"2024-08-16T00:00:00Z","timestamp":1723766400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China","award":["81773787"],"award-info":[{"award-number":["81773787"]}]},{"name":"National Natural Science Foundation of China","award":["82003815"],"award-info":[{"award-number":["82003815"]}]},{"name":"National Natural Science Foundation of China","award":["2019B020202002"],"award-info":[{"award-number":["2019B020202002"]}]},{"name":"National Natural Science Foundation of China","award":["ZZ13-035-02"],"award-info":[{"award-number":["ZZ13-035-02"]}]},{"name":"National Natural Science Foundation of China","award":["2019XZZX-LG04"],"award-info":[{"award-number":["2019XZZX-LG04"]}]},{"name":"Major scientific and technological projects of Guangdong Province","award":["81773787"],"award-info":[{"award-number":["81773787"]}]},{"name":"Major scientific and technological projects of Guangdong Province","award":["82003815"],"award-info":[{"award-number":["82003815"]}]},{"name":"Major scientific and technological projects of Guangdong Province","award":["2019B020202002"],"award-info":[{"award-number":["2019B020202002"]}]},{"name":"Major scientific and technological projects of Guangdong Province","award":["ZZ13-035-02"],"award-info":[{"award-number":["ZZ13-035-02"]}]},{"name":"Major scientific and technological projects of Guangdong Province","award":["2019XZZX-LG04"],"award-info":[{"award-number":["2019XZZX-LG04"]}]},{"name":"Chinese Academy of Traditional Chinese Medicine","award":["81773787"],"award-info":[{"award-number":["81773787"]}]},{"name":"Chinese Academy of Traditional Chinese Medicine","award":["82003815"],"award-info":[{"award-number":["82003815"]}]},{"name":"Chinese Academy of Traditional Chinese Medicine","award":["2019B020202002"],"award-info":[{"award-number":["2019B020202002"]}]},{"name":"Chinese Academy of Traditional Chinese Medicine","award":["ZZ13-035-02"],"award-info":[{"award-number":["ZZ13-035-02"]}]},{"name":"Chinese Academy of Traditional Chinese Medicine","award":["2019XZZX-LG04"],"award-info":[{"award-number":["2019XZZX-LG04"]}]},{"name":"State Administration of Traditional Chinese Medicine","award":["81773787"],"award-info":[{"award-number":["81773787"]}]},{"name":"State Administration of Traditional Chinese Medicine","award":["82003815"],"award-info":[{"award-number":["82003815"]}]},{"name":"State Administration of Traditional Chinese Medicine","award":["2019B020202002"],"award-info":[{"award-number":["2019B020202002"]}]},{"name":"State Administration of Traditional Chinese Medicine","award":["ZZ13-035-02"],"award-info":[{"award-number":["ZZ13-035-02"]}]},{"name":"State Administration of Traditional Chinese Medicine","award":["2019XZZX-LG04"],"award-info":[{"award-number":["2019XZZX-LG04"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>The cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-dependent Cl\u2212 channel, is closely associated with multiple pathogen infections, such as SARS-CoV-2. However, whether the function of the CFTR is involved in herpes simplex virus (HSV) infection has not been reported. To evaluate the association of CFTR activity with HSV infection, the antiviral effect of CFTR inhibitors in epithelial cells and HSV-infected mice was tested in this study. The data showed that treatment with CFTR inhibitors in different concentrations, Glyh-101 (5\u201320 \u03bcM), CFTRi-172 (5\u201320 \u03bcM) and IOWH-032 (5\u201320 \u03bcM), or the gene silence of the CFTR could suppress herpes simplex virus 1 (HSV-1) and herpes simplex virus 2 (HSV-2) replication in human HaCaT keratinocytes cells, and that a CFTR inhibitor, Glyh-101 (10\u201320 \u03bcM), protected mice from HSV-1 and HSV-2 infection. Intracellular Cl\u2212 concentration ([Cl\u2212]i) was decreased after HSV infection via the activation of adenylyl cyclase (AC)-cAMP signaling pathways. CFTR inhibitors (20 \u03bcM) increased the reduced [Cl\u2212]i caused by HSV infection in host epithelial cells. Additionally, CFTR inhibitors reduced the activity and phosphorylation of SGK1 in infected cells and tissues (from the eye and vagina). Our study found that CFTR inhibitors can effectively suppress HSV-1 and HSV-2 infection, revealing a previously unknown role of CFTR inhibitors in HSV infection and suggesting new perspectives on the mechanisms governing HSV infection in host epithelial cells, as well as leading to potential novel treatments.<\/jats:p>","DOI":"10.3390\/v16081308","type":"journal-article","created":{"date-parts":[[2024,8,16]],"date-time":"2024-08-16T12:40:07Z","timestamp":1723812007000},"page":"1308","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["CFTR Inhibitors Display Antiviral Activity against Herpes Simplex Virus"],"prefix":"10.3390","volume":"16","author":[{"given":"Ping","family":"Jiang","sequence":"first","affiliation":[{"name":"Guangdong Provincial Key Laboratory of New Drug Screening, Guangzhou Key Laboratory of Drug Research for Emerging Virus Prevention and Treatment, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China"},{"name":"Guangdong Key Laboratory for Research and Development of Natural Drugs, Dongguan Key Laboratory of Traditional Chinese Medicine and New Pharmaceutical Development, School of Pharmacy, Guangdong Medical University, Dongguan 523808, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhong","family":"Dai","sequence":"additional","affiliation":[{"name":"Guangdong Key Laboratory for Research and Development of Natural Drugs, Dongguan Key Laboratory of Traditional Chinese Medicine and New Pharmaceutical Development, School of Pharmacy, Guangdong Medical University, Dongguan 523808, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chan","family":"Yang","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of New Drug Screening, Guangzhou Key Laboratory of Drug Research for Emerging Virus Prevention and Treatment, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liqiong","family":"Ding","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Hubei University of Science and Technology, Xianning 437100, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Songshan","family":"Li","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of New Drug Screening, Guangzhou Key Laboratory of Drug Research for Emerging Virus Prevention and Treatment, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinfeng","family":"Xu","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of New Drug Screening, Guangzhou Key Laboratory of Drug Research for Emerging Virus Prevention and Treatment, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chen","family":"Cheng","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of New Drug Screening, Guangzhou Key Laboratory of Drug Research for Emerging Virus Prevention and Treatment, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinshen","family":"Wang","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of New Drug Screening, Guangzhou Key Laboratory of Drug Research for Emerging Virus Prevention and Treatment, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6346-5006","authenticated-orcid":false,"given":"Shuwen","family":"Liu","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of New Drug Screening, Guangzhou Key Laboratory of Drug Research for Emerging Virus Prevention and Treatment, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China"},{"name":"State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Southern Medical University, Guangzhou 510515, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"104721","DOI":"10.1016\/j.antiviral.2020.104721","article-title":"Prevention and treatment of neonatal herpes simplex virus infection","volume":"176","author":"Samies","year":"2020","journal-title":"Antivir. 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