{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T11:02:00Z","timestamp":1789642920864,"version":"4.0.0"},"reference-count":32,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science and Technology Council","award":["NSTC112-2320-B-039-054-MY3"],"award-info":[{"award-number":["NSTC112-2320-B-039-054-MY3"]}]},{"name":"National Science and Technology Council","award":["NSTC113-2320-B-A49-024"],"award-info":[{"award-number":["NSTC113-2320-B-A49-024"]}]},{"name":"National Science and Technology Council","award":["NSTC112-2320-B-A49-044"],"award-info":[{"award-number":["NSTC112-2320-B-A49-044"]}]},{"name":"China Medical University","award":["CMU-DDC-TD3-2"],"award-info":[{"award-number":["CMU-DDC-TD3-2"]}]},{"name":"China Medical University","award":["CMU114-ASIA-04"],"award-info":[{"award-number":["CMU114-ASIA-04"]}]},{"name":"China Medical University","award":["CMU114-MF-44"],"award-info":[{"award-number":["CMU114-MF-44"]}]},{"name":"Drug Development Center, China Medical University","award":["CMU-DDC-TD3-2"],"award-info":[{"award-number":["CMU-DDC-TD3-2"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Maraviroc (MVC), a CCR5 antagonist, has been proposed as a potential antiviral agent against SARS-CoV-2; however, its mechanism of action across viral variants remains unclear. Here, we evaluated the antiviral activity of MVC against SARS-CoV-2 wild-type (WT) and Omicron BA.1 variants using single-round infectious particles (SRIPs), virus-like particles (VLPs), and cell-based assays, with a focus on its impact on viral entry and Mpro function. MVC potently inhibited infection of both WT and BA.1 SRIPs in Vero E6 cells, exhibiting EC50 values of 0.0065 \u03bcM and 0.016 \u03bcM, respectively. Time-of-addition assays revealed that MVC primarily targets the early phase of infection, with the strongest inhibition observed at the viral entry stage, while moderate effects were detected during attachment and post-entry stages. Fluorescence-labeled VLP imaging demonstrated distinct entry pathways, with WT predominantly entering via plasma membrane fusion and BA.1 via endocytosis, independent of cell type. MVC altered WT-VLP trafficking by promoting internalization and lysosomal localization, whereas it had minimal impact on BA.1 internalization. In spike-mediated cell\u2013cell fusion assays, MVC preferentially inhibited WT spike-driven syncytium formation but showed limited effects on BA.1 or BA.4 fusion, while more effectively reducing Omicron spike-mediated binding. At the post-entry stage, MVC inhibited SARS-CoV-2 main protease (Mpro) activity, with BA.1 Mpro (P132H) exhibiting greater sensitivity (IC50 = 0.496 \u00b5M) than WT (1.869 \u00b5M). Collectively, these findings demonstrate that MVC exerts variant-dependent antiviral effects by targeting viral entry, modulating trafficking pathways, and inhibiting Mpro activity. This study highlights MVC as a multi-stage inhibitor with differential efficacy against SARS-CoV-2 variants, providing insights into its potential therapeutic application.<\/jats:p>","DOI":"10.3390\/v18080911","type":"journal-article","created":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T11:04:12Z","timestamp":1787137452000},"page":"911","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Maraviroc Inhibits SARS-CoV-2 Through Variant-Dependent Effects on Viral Entry and Mpro Activity Using Single-Round Infectious Particle and Virus-like Particle Models"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-6784-6646","authenticated-orcid":false,"given":"Uyen Nguyen Phuong","family":"Le","sequence":"first","affiliation":[{"name":"Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung 404328, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Po-Ju","family":"Chen","sequence":"additional","affiliation":[{"name":"Department and Institute of Pharmacology, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6291-4436","authenticated-orcid":false,"given":"Li-Wei","family":"Chu","sequence":"additional","affiliation":[{"name":"Department and Institute of Pharmacology, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane Cynthia","family":"Arifin","sequence":"additional","affiliation":[{"name":"Department and Institute of Pharmacology, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih-Hao","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Internal Medicine, China Medical University Hospital, China Medical University, Taichung 404327, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-2311-5480","authenticated-orcid":false,"given":"Yu-Hsuan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department and Institute of Pharmacology, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Chi","family":"Su","sequence":"additional","affiliation":[{"name":"Graduate Institute of Biomedical Sciences, China Medical University, Taichung 404328, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Po-Ren","family":"Hsueh","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Internal Medicine, China Medical University Hospital, China Medical University, Taichung 404327, Taiwan"},{"name":"Department of Laboratory Medicine, China Medical University Hospital, Taichung 404327, Taiwan"},{"name":"School of Medicine, China Medical University, Taichung 404328, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2604-9913","authenticated-orcid":false,"given":"Yueh-Hsin","family":"Ping","sequence":"additional","affiliation":[{"name":"Department and Institute of Pharmacology, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan"},{"name":"Institute of Biophotonics, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0165-2652","authenticated-orcid":false,"given":"Cheng-Wen","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung 404328, Taiwan"},{"name":"Graduate Institute of Biomedical Sciences, China Medical University, Taichung 404328, Taiwan"},{"name":"Office of Research and Development, Asia University, Taichung 413305, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"ftaa042","DOI":"10.1093\/femspd\/ftaa042","article-title":"Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a newly emerged pathogen: An overview","volume":"78","author":"Rathore","year":"2020","journal-title":"Pathog. 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