Natural apocarotenoids and their synthetic glycopeptide conjugates inhibit SARS-CoV-2 replication

Bereczki, Ilona (author), Kos, Janko (author), Herczegh, Pál (author), Borbás, Anikó (author)

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.

• Language: English
• Keywords: teicoplanin, ristocetin, bixin, crocetin, β-apocarotenoic acid, SARS-CoV-2, antiviral activity, antibacterial activity
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FFA - Faculty of Pharmacy
• Publication status: Published
• Publication version: Version of Record
• Year: 2021
• Number of pages: 25 str.
• Numbering: Vol. 14, iss. 11, art. 1111
• PID: 20.500.12556/RUL-136426
• UDC: 577
• ISSN on article: 1424-8247
• DOI: 10.3390/ph14111111
• COBISS.SI-ID: 83004931
• Publication date in RUL: 03.05.2022

BERECZKI, Ilona, KOS, Janko, HERCZEGH, Pál and BORBÁS, Anikó, 2021, Natural apocarotenoids and their synthetic glycopeptide conjugates inhibit SARS-CoV-2 replication. Pharmaceuticals [online]. 2021. Vol. 14, no. 11,  1111. [Accessed 13 August 2025]. DOI 10.3390/ph14111111. Retrieved from: https://repozitorij.uni-lj.si/IzpisGradiva.php?lang=eng&id=136426

Record is a part of a journal

• Title: Pharmaceuticals
• Shortened title: Pharmaceuticals
• Publisher: MDPI
• ISSN: 1424-8247
• COBISS.SI-ID: 517582617

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• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.
• Licensing start date: 01.11.2021