{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T23:03:14Z","timestamp":1788217394514,"version":"build-2803163510"},"reference-count":45,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2023,7,8]],"date-time":"2023-07-08T00:00:00Z","timestamp":1688774400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research Development and Innovation Office (NKFIH, OTKA)","award":["FK 128751"],"award-info":[{"award-number":["FK 128751"]}]},{"name":"National Research Development and Innovation Office (NKFIH, OTKA)","award":["K 138518"],"award-info":[{"award-number":["K 138518"]}]},{"name":"National Research Development and Innovation Office (NKFIH, OTKA)","award":["PC2022-7\/2022"],"award-info":[{"award-number":["PC2022-7\/2022"]}]},{"name":"Hungarian Academy of Sciences","award":["FK 128751"],"award-info":[{"award-number":["FK 128751"]}]},{"name":"Hungarian Academy of Sciences","award":["K 138518"],"award-info":[{"award-number":["K 138518"]}]},{"name":"Hungarian Academy of Sciences","award":["PC2022-7\/2022"],"award-info":[{"award-number":["PC2022-7\/2022"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Orally administered small molecules may have important therapeutic potential in treating COVID-19 disease. The recently developed antiviral agents, Molnupiravir and Nirmatrelvir, have been reported to be efficient treatments, with only moderate side effects, especially when applied in the early phases of this disease. However, drug\u2013drug and drug\u2013transporter interactions have already been noted by the drug development companies and in the application notes. In the present work, we have studied some of the key human transporters interacting with these agents. The nucleoside analog Molnupiravir (EIDD-2801) and its main metabolite (EIDD-1931) were found to inhibit CNT1,2 in addition to the ENT1,2 nucleoside transporters; however, it did not significantly influence the relevant OATP transporters or the ABCC4 nucleoside efflux transporter. The active component of Paxlovid (PF-07321332, Nirmatrelvir) inhibited the function of several OATPs and of ABCB1 but did not affect ABCG2. However, significant inhibition was observed only at high concentrations of Nirmatrelvir and probably did not occur in vivo. Paxlovid, as used in the clinic, is a combination of Nirmatrelvir (viral protease inhibitor) and Ritonavir (a \u201cbooster\u201d inhibitor of Nirmatrelvir metabolism). Ritonavir is known to inhibit several drug transporters; therefore, we have examined these compounds together, in relevant concentrations and ratios. No additional inhibitory effect of Nirmatrelvir was observed compared to the strong transporter inhibition caused by Ritonavir. Our current in vitro results should help to estimate the potential drug\u2013drug interactions of these newly developed agents during COVID-19 treatment.<\/jats:p>","DOI":"10.3390\/ijms241411237","type":"journal-article","created":{"date-parts":[[2023,7,10]],"date-time":"2023-07-10T00:35:21Z","timestamp":1688949321000},"page":"11237","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Interactions of the Anti-SARS-CoV-2 Agents Molnupiravir and Nirmatrelvir\/Paxlovid with Human Drug Transporters"],"prefix":"10.3390","volume":"24","author":[{"given":"\u00c9va","family":"Bakos","sequence":"first","affiliation":[{"name":"Research Centre for Natural Sciences\u2014RCNS, Magyar Tud\u00f3sok krt 2, 1117 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Csilla","family":"Temesszentandr\u00e1si-Ambrus","sequence":"additional","affiliation":[{"name":"Charles River Laboratories, Irinyi J\u00f3zsef u. 4-20, 1117 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9721-6339","authenticated-orcid":false,"given":"Csilla","family":"\u00d6zvegy-Laczka","sequence":"additional","affiliation":[{"name":"Research Centre for Natural Sciences\u2014RCNS, Magyar Tud\u00f3sok krt 2, 1117 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zsuzsanna","family":"G\u00e1borik","sequence":"additional","affiliation":[{"name":"Charles River Laboratories, Irinyi J\u00f3zsef u. 4-20, 1117 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0592-4539","authenticated-orcid":false,"given":"Bal\u00e1zs","family":"Sarkadi","sequence":"additional","affiliation":[{"name":"Research Centre for Natural Sciences\u2014RCNS, Magyar Tud\u00f3sok krt 2, 1117 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0972-4606","authenticated-orcid":false,"given":"\u00c1gnes","family":"Telbisz","sequence":"additional","affiliation":[{"name":"Research Centre for Natural Sciences\u2014RCNS, Magyar Tud\u00f3sok krt 2, 1117 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Painter, W.P., Holman, W., Bush, J.A., Almazedi, F., Malik, H., Eraut, N., Morin, M.J., Szewczyk, L.J., and Painter, G.R. 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