{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T12:13:39Z","timestamp":1790424819126,"version":"4.1.0"},"reference-count":76,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T00:00:00Z","timestamp":1675296000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research, Development and Innovation Office-NKFIA (Hungary)","award":["PD 131472"],"award-info":[{"award-number":["PD 131472"]}]},{"name":"National Research, Development and Innovation Office-NKFIA (Hungary)","award":["TKP-2021-EGA-32"],"award-info":[{"award-number":["TKP-2021-EGA-32"]}]},{"name":"National Research, Development and Innovation Office-NKFIA (Hungary)","award":["bo-125-20"],"award-info":[{"award-number":["bo-125-20"]}]},{"name":"National Research, Development and Innovation Office-NKFIA (Hungary)","award":["LP2019\u20136\/2019"],"award-info":[{"award-number":["LP2019\u20136\/2019"]}]},{"name":"J. Bolyai Research Fellowship","award":["PD 131472"],"award-info":[{"award-number":["PD 131472"]}]},{"name":"J. Bolyai Research Fellowship","award":["TKP-2021-EGA-32"],"award-info":[{"award-number":["TKP-2021-EGA-32"]}]},{"name":"J. Bolyai Research Fellowship","award":["bo-125-20"],"award-info":[{"award-number":["bo-125-20"]}]},{"name":"J. Bolyai Research Fellowship","award":["LP2019\u20136\/2019"],"award-info":[{"award-number":["LP2019\u20136\/2019"]}]},{"name":"\u2018Lend\u00fclet\u2019 Programme","award":["PD 131472"],"award-info":[{"award-number":["PD 131472"]}]},{"name":"\u2018Lend\u00fclet\u2019 Programme","award":["TKP-2021-EGA-32"],"award-info":[{"award-number":["TKP-2021-EGA-32"]}]},{"name":"\u2018Lend\u00fclet\u2019 Programme","award":["bo-125-20"],"award-info":[{"award-number":["bo-125-20"]}]},{"name":"\u2018Lend\u00fclet\u2019 Programme","award":["LP2019\u20136\/2019"],"award-info":[{"award-number":["LP2019\u20136\/2019"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>There are a number of uncertainties regarding plasma protein binding and blood distribution of the active drugs favipiravir (FAVI), molnupiravir (MOLNU) and imatinib (IMA), which were recently proposed as therapeutics for the treatment of COVID-19 disease. Therefore, proton dissociation processes, solubility, lipophilicity, and serum protein binding of these three substances were investigated in detail. The drugs display various degrees of lipophilicity at gastric (pH 2.0) and blood pH (pH 7.4). The determined pKa values explain well the changes in lipophilic character of the respective compounds. The serum protein binding was studied by membrane ultrafiltration, frontal analysis capillary electrophoresis, steady-state fluorometry, and fluorescence anisotropy techniques. The studies revealed that the ester bond in MOLNU is hydrolyzed by protein constituents of blood serum. Molnupiravir and its hydrolyzed form do not bind considerably to blood proteins. Likewise, FAVI does not bind to human serum albumin (HSA) and \u03b11-acid glycoprotein (AGP) and shows relatively weak binding to the protein fraction of whole blood serum. Imatinib binds to AGP with high affinity (logK\u2032 = 5.8\u20136.0), while its binding to HSA is much weaker (logK\u2032 \u2264 4.0). The computed constants were used to model the distribution of IMA in blood plasma under physiological and \u2018acute-phase\u2019 conditions as well.<\/jats:p>","DOI":"10.3390\/ijms24032849","type":"journal-article","created":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T02:57:24Z","timestamp":1675306644000},"page":"2849","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Evaluation of In Vitro Distribution and Plasma Protein Binding of Selected Antiviral Drugs (Favipiravir, Molnupiravir and Imatinib) against SARS-CoV-2"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8736-3215","authenticated-orcid":false,"given":"Orsolya","family":"D\u00f6m\u00f6t\u00f6r","sequence":"first","affiliation":[{"name":"MTA-SZTE Lend\u00fclet Functional Metal Complexes Research Group, Department of Inorganic and Analytical Chemistry, Interdisciplinary Excellence Centre, University of Szeged, D\u00f3m t\u00e9r 7, H-6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8058-8128","authenticated-orcid":false,"given":"\u00c9va A.","family":"Enyedy","sequence":"additional","affiliation":[{"name":"MTA-SZTE Lend\u00fclet Functional Metal Complexes Research Group, Department of Inorganic and Analytical Chemistry, Interdisciplinary Excellence Centre, University of Szeged, D\u00f3m t\u00e9r 7, H-6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1056\/NEJMoa2116044","article-title":"Molnupiravir for Oral Treatment of COVID-19 in Nonhospitalized Patients","volume":"386","author":"Bernal","year":"2021","journal-title":"N. 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