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In part, this is linked to resistance, cost and restrictions on use in several patient settings. More generally, it remains attractive to increase our arsenal of anti-viral approaches to target HCMV. We previously characterized a potent inhibitor of HCMV infection, DIDS, that displays cysteine reactivity, allowing it to bind virions and neutralize HCMV infection of fibroblasts. We now show that DIDS is inhibitory to cell-free and cell-associated infection of multiple cell types, including cells of the haematopoietic lineage\u2014cells important for latency and dissemination. Consistent with this broad activity, DIDS partially inhibited gB (but not SARS-CoV-2 spike) fusion activity. Intriguingly, further characterization of DIDS activity in myeloid cells revealed that, unlike in all other cell types, DIDS blocked a post-entry event in CD14+ monocytes and also dendritic cell derivatives. Despite viral entry, entry was largely silent, with a failure to activate innate immunity and cell survival pathways known to be activated by HCMV. In contrast, HCMV infection was observed to activate host miRNA expression in CD14+ cells, suggesting a DIDS-insensitive viral function was responsible or, alternatively, that host miRNA expression is a potential anti-viral response to viral internalization. Thus, we report the further characterization of a broad-acting inhibitor of HCMV infection, which may also prove a useful tool to study unique events for the infection of monocytic cells by HCMV\u2014a cell type that is crucial for HCMV dissemination and pathogenesis in vivo.<\/jats:p>","DOI":"10.3390\/pathogens15050520","type":"journal-article","created":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T15:17:23Z","timestamp":1779203843000},"page":"520","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Potent Inhibitor of Human Cytomegalovirus Infection Works Post-Entry Specifically in Differentiating Myelo-Monocytic Cells"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0379-7161","authenticated-orcid":false,"given":"Matthew J.","family":"Murray","sequence":"first","affiliation":[{"name":"Institute of Infection, Immunity & Transplantation, Royal Free Campus, University College London (UCL), London NW3 2PP, UK"},{"name":"Novo Nordisk Foundation Center for Protein Research, Department of Molecular and Cellular Medicine, University of Copenhagen, DK-2200 Copenhagen, Denmark"},{"name":"Danish Cancer Institute, Danish Cancer Society, DK-2100 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7156-1521","authenticated-orcid":false,"given":"Alexander","family":"Hargreaves","sequence":"additional","affiliation":[{"name":"Institute of Infection, Immunity & Transplantation, Royal Free Campus, University College London (UCL), London NW3 2PP, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleanor","family":"Bradley","sequence":"additional","affiliation":[{"name":"Institute of Infection, Immunity & Transplantation, Royal Free Campus, University College London (UCL), London NW3 2PP, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Lee","sequence":"additional","affiliation":[{"name":"Institute of Infection, Immunity & Transplantation, Royal Free Campus, University College London (UCL), London NW3 2PP, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanjing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Infection, Immunity & Transplantation, Royal Free Campus, University College London (UCL), London NW3 2PP, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Reuter","sequence":"additional","affiliation":[{"name":"Harald zur Hausen Institute of Virology, University Hospital Erlangen, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg (FAU), 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4820-2712","authenticated-orcid":false,"given":"Marco","family":"Thomas","sequence":"additional","affiliation":[{"name":"Harald zur Hausen Institute of Virology, University Hospital Erlangen, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg (FAU), 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4909-1076","authenticated-orcid":false,"given":"Matthew B.","family":"Reeves","sequence":"additional","affiliation":[{"name":"Institute of Infection, Immunity & Transplantation, Royal Free Campus, University College London (UCL), London NW3 2PP, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1038\/s41579-021-00582-z","article-title":"Pathogenesis of human cytomegalovirus in the immunocompromised host","volume":"19","author":"Griffiths","year":"2021","journal-title":"Nat. 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