{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T08:29:51Z","timestamp":1768552191014,"version":"3.49.0"},"reference-count":124,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,4,23]],"date-time":"2023-04-23T00:00:00Z","timestamp":1682208000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Academy of Scientific Research and Technology (ASRT)","award":["RESPECT-2021-9999"],"award-info":[{"award-number":["RESPECT-2021-9999"]}]},{"name":"Academy of Scientific Research and Technology (ASRT)","award":["IP7-FDMZ-2022"],"award-info":[{"award-number":["IP7-FDMZ-2022"]}]},{"name":"Croatian Ministry of Science and Education","award":["RESPECT-2021-9999"],"award-info":[{"award-number":["RESPECT-2021-9999"]}]},{"name":"Croatian Ministry of Science and Education","award":["IP7-FDMZ-2022"],"award-info":[{"award-number":["IP7-FDMZ-2022"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) canonically utilizes clathrin-mediated endocytosis (CME) and several other endocytic mechanisms to invade airway epithelial cells. Endocytic inhibitors, particularly those targeting CME-related proteins, have been identified as promising antiviral drugs. Currently, these inhibitors are ambiguously classified as chemical, pharmaceutical, or natural inhibitors. However, their varying mechanisms may suggest a more realistic classification system. Herein, we present a new mechanistic-based classification of endocytosis inhibitors, in which they are segregated among four distinct classes including: (i) inhibitors that disrupt endocytosis-related protein\u2013protein interactions, and assembly or dissociation of complexes; (ii) inhibitors of large dynamin GTPase and\/or kinase\/phosphatase activities associated with endocytosis; (iii) inhibitors that modulate the structure of subcellular components, especially the plasma membrane, and actin; and (iv) inhibitors that cause physiological or metabolic alterations in the endocytosis niche. Excluding antiviral drugs designed to halt SARS-CoV-2 replication, other drugs, either FDA-approved or suggested through basic research, could be systematically assigned to one of these classes. We observed that many anti-SARS-CoV-2 drugs could be included either in class III or IV as they interfere with the structural or physiological integrity of subcellular components, respectively. This perspective may contribute to our understanding of the relative efficacy of endocytosis-related inhibitors and support the optimization of their individual or combined antiviral potential against SARS-CoV-2. However, their selectivity, combined effects, and possible interactions with non-endocytic cellular targets need more clarification.<\/jats:p>","DOI":"10.3390\/v15051040","type":"journal-article","created":{"date-parts":[[2023,4,24]],"date-time":"2023-04-24T01:35:44Z","timestamp":1682300144000},"page":"1040","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Mechanistic-Based Classification of Endocytosis-Related Inhibitors: Does It Aid in Assigning Drugs against SARS-CoV-2?"],"prefix":"10.3390","volume":"15","author":[{"given":"Mohamed","family":"Hessien","sequence":"first","affiliation":[{"name":"Molecular Cell Biology Unit, Division of Biochemistry, Department of Chemistry, Faculty of Science, Tanta University, Tanta 31527, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1629-1290","authenticated-orcid":false,"given":"Thoria","family":"Donia","sequence":"additional","affiliation":[{"name":"Molecular Cell Biology Unit, Division of Biochemistry, Department of Chemistry, Faculty of Science, Tanta University, Tanta 31527, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashraf A.","family":"Tabll","sequence":"additional","affiliation":[{"name":"National Research Centre, Microbial Biotechnology Department, Biotechnology Research Institute, Giza 12622, Egypt"},{"name":"Egypt Center for Research and Regenerative Medicine (ECRRM), Cairo 11517, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eiman","family":"Adly","sequence":"additional","affiliation":[{"name":"Molecular Cell Biology Unit, Division of Biochemistry, Department of Chemistry, Faculty of Science, Tanta University, Tanta 31527, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tawfeek H.","family":"Abdelhafez","sequence":"additional","affiliation":[{"name":"National Research Centre, Microbial Biotechnology Department, Biotechnology Research Institute, Giza 12622, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amany","family":"Attia","sequence":"additional","affiliation":[{"name":"Molecular Cell Biology Unit, Division of Biochemistry, Department of Chemistry, Faculty of Science, Tanta University, Tanta 31527, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7303-1444","authenticated-orcid":false,"given":"Samar Sami","family":"Alkafaas","sequence":"additional","affiliation":[{"name":"Molecular Cell Biology Unit, Division of Biochemistry, Department of Chemistry, Faculty of Science, Tanta University, Tanta 31527, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucija","family":"Kuna","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Biochemistry, Faculty of Dental Medicine and Health Osijek, University of J. J. Strossmayer Osijek, 31000 Osijek, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marija","family":"Glasnovic","sequence":"additional","affiliation":[{"name":"Department of Medicine, Family Medicine and History of Medicine, Faculty of Medicine Osijek, University of J. J. Strossmayer Osijek, 31000 Osijek, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vesna","family":"Cosic","sequence":"additional","affiliation":[{"name":"Department of Paediatrics and Gynaecology with Obstetrics, Faculty of Dental Medicine and Health Osijek, University of J. J. Strossmayer Osijek, 31000 Osijek, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Smolic","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Biochemistry, Faculty of Dental Medicine and Health Osijek, University of J. J. Strossmayer Osijek, 31000 Osijek, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6867-826X","authenticated-orcid":false,"given":"Martina","family":"Smolic","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Biochemistry, Faculty of Dental Medicine and Health Osijek, University of J. J. Strossmayer Osijek, 31000 Osijek, Croatia"},{"name":"Department of Pharmacology, Faculty of Medicine Osijek, University of Osijek, 31000 Osijek, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1186\/1743-422X-10-177","article-title":"Multiscale perspectives of virus entry via endocytosis","volume":"10","author":"Barrow","year":"2013","journal-title":"Virol. 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