20.500.12556/RUL-136426 Natural apocarotenoids and their synthetic glycopeptide conjugates inhibit SARS-CoV-2 replication The protracted global COVID-19 pandemic urges the development of new drugs against the causative agent SARS-CoV-2. The clinically used glycopeptide antibiotic, teicoplanin, emerged as a potential antiviral, and its efficacy was improved with lipophilic modifications. This prompted us to prepare new lipophilic apocarotenoid conjugates of teicoplanin, its pseudoaglycone and the related ristocetin aglycone. Their antiviral effect was tested against SARS-CoV-2 in Vero E6 cells, using a cell viability assay and quantitative PCR of the viral RNA, confirming their micromolar inhibitory activity against viral replication. Interestingly, two of the parent apocarotenoids, bixin and β-apo-8′carotenoic acid, exerted remarkable anti-SARS-CoV-2 activity. Mechanistic studies involved cathepsin L and B, as well as the main protease 3CLPro, and the results were rationalized by computational studies. Glycopeptide conjugates show dual inhibitory action, while apocarotenoids have mostly cathepsin B and L affinity. Since teicoplanin is a marketed antibiotic and the natural bixin is an approved, cheap and widely used red colorant food additive, these readily available compounds and their conjugates as potential antivirals are worthy of further exploration. teicoplanin ristocetin bixin crocetin β-apocarotenoic acid SARS-CoV-2 antiviral activity antibacterial activity true false true Angleški jezik Ni določen Članek v reviji 2022-05-03 14:03:16 2022-05-03 14:03:21 2022-09-15 04:13:52 0000-00-00 00:00:00 2021 0 0 25 str. iss. 11, art. 1111 Vol. 14 2021 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 577 1424-8247 10.3390/ph14111111 83004931 pharmaceuticals-14-01111-v2.pdf pharmaceuticals-14-01111-v2.pdf 1 608FB1C8455CF41F0BB58187C44CB5BA 87d1697c99aabb78260b409ad42b97528e929cfc5b8781f2b5d0e90b88eb600f 3426e741-cad9-11ec-8aca-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=156072 https://www.mdpi.com/1424-8247/14/11/1111 1 eff9695f-cad8-11ec-8aca-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=156071 Fakulteta za farmacijo 0 0 0