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Established antiviral drugs, such as acyclovir (ACV), have been successfully used over the past decades. However, due to growing viral resistance against approved antivirals and the lack of effective vaccines, new concepts are essential to target HSV-1 infections. Here, we present data on the inhibitory effect of the procaine-based substance ProcCluster\u00ae (PC) in reducing HSV-1 replication in vitro. Non-toxic PC concentrations significantly decreased HSV-1 replication in infected cells. Immunofluorescence microscopy revealed an accumulation of viral proteins in early and recycling endosomes, resulting in reduced viral release. The combination of PC with ACV resulted in an enhanced antiviral effect. Based on these results, PC alone, as well as in combination with ACV, appears to be a promising substance with antiviral potential against HSV-1 infections.<\/jats:p>","DOI":"10.3390\/ijms26157185","type":"journal-article","created":{"date-parts":[[2025,7,25]],"date-time":"2025-07-25T11:38:41Z","timestamp":1753443521000},"page":"7185","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Procaine-Based ProcCluster\u00ae Impedes the Second Envelopment Process of Herpes Simplex Virus Type 1"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-5917-9527","authenticated-orcid":false,"given":"Johannes","family":"Jungwirth","sequence":"first","affiliation":[{"name":"Section of Experimental Virology, Institute of Medical Microbiology, Center for Molecular Biomedicine (CMB), Jena University Hospital, Hans-Knoell-Str. 2, D-07745 Jena, Germany"},{"name":"Institute of Toxicology, University Medical Center of the Johannes Gutenberg University Mainz, Obere Zahlbacher Str. 67, D-55131 Mainz, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa","family":"Siegert","sequence":"additional","affiliation":[{"name":"Section of Experimental Virology, Institute of Medical Microbiology, Center for Molecular Biomedicine (CMB), Jena University Hospital, Hans-Knoell-Str. 2, D-07745 Jena, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-3456-7737","authenticated-orcid":false,"given":"Lena","family":"Gauthier","sequence":"additional","affiliation":[{"name":"Section of Experimental Virology, Institute of Medical Microbiology, Center for Molecular Biomedicine (CMB), Jena University Hospital, Hans-Knoell-Str. 2, D-07745 Jena, Germany"},{"name":"Department Biophysical Imaging, Leibniz Institute of Photonic Technology (IPHT), Member of the Leibniz Center for Photonics in Infection Research (LPI), Albert-Einstein-Str. 9, D-07745 Jena, Germany"},{"name":"Institute of Applied Optics and Biophysics, Friedrich Schiller University Jena, Max-Wien-Platz 1, D-07743 Jena, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas","family":"Henke","sequence":"additional","affiliation":[{"name":"Section of Experimental Virology, Institute of Medical Microbiology, Center for Molecular Biomedicine (CMB), Jena University Hospital, Hans-Knoell-Str. 2, D-07745 Jena, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3973-045X","authenticated-orcid":false,"given":"Oliver H.","family":"Kr\u00e4mer","sequence":"additional","affiliation":[{"name":"Institute of Toxicology, University Medical Center of the Johannes Gutenberg University Mainz, Obere Zahlbacher Str. 67, D-55131 Mainz, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beatrice","family":"Engert","sequence":"additional","affiliation":[{"name":"inflamed pharma GmbH, Winzerlaer Str. 2, D-07745 Jena, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8879-6087","authenticated-orcid":false,"given":"Christina","family":"Ehrhardt","sequence":"additional","affiliation":[{"name":"Section of Experimental Virology, Institute of Medical Microbiology, Center for Molecular Biomedicine (CMB), Jena University Hospital, Hans-Knoell-Str. 2, D-07745 Jena, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,25]]},"reference":[{"key":"ref_1","unstructured":"Mahy, B.W.J., and Van Regenmortel, M.H.V. 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