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Article

Natural Apocarotenoids and Their Synthetic Glycopeptide Conjugates Inhibit SARS-CoV-2 Replication

1
Department of Pharmaceutical Chemistry, University of Debrecen, Egyetem tér 1, H-4032 Debrecen, Hungary
2
Szentágothai Research Centre, National Laboratory of Virology, Ifjúság útja 20, H-7624 Pécs, Hungary
3
Institute of Biology, Faculty of Sciences, University of Pécs, Ifjúság útja 6, H-7624 Pécs, Hungary
4
Department of Biochemistry and Medical Chemistry, Medical School, University of Pécs, Szigeti u. 12, H-7624 Pécs, Hungary
5
Department of Organic Chemistry, University of Debrecen, H-4032 Debrecen, Hungary
6
Department of Medical Microbiology, Semmelweis University, Nagyvárad tér 4, H-1089 Budapest, Hungary
7
Department of Biotechnology, Jožef Stefan Institute, Jamova 39, 1000 Ljubljana, Slovenia
8
Faculty of Pharmacy, University of Ljubljana, Aškerčeva cesta 7, 1000 Ljubljana, Slovenia
9
TargetEx Ltd., Madách Imre Utca 31/2, H-2120 Dunakeszi, Hungary
10
Research Centre for Natural Sciences, Medicinal Chemistry Research Group, Magyar Tudósok krt. 2, H-1117 Budapest, Hungary
11
Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Flemingovo nam. 2, CZ-16000 Prague, Czech Republic
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: María Jesús Pérez Pérez
Pharmaceuticals 2021, 14(11), 1111; https://doi.org/10.3390/ph14111111
Received: 1 October 2021 / Revised: 26 October 2021 / Accepted: 26 October 2021 / Published: 30 October 2021
(This article belongs to the Special Issue Glycopeptide Antibiotics 2021)
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. View Full-Text
Keywords: teicoplanin; ristocetin; bixin; crocetin; β-apocarotenoic acid; SARS-CoV-2; antiviral activity; antibacterial activity teicoplanin; ristocetin; bixin; crocetin; β-apocarotenoic acid; SARS-CoV-2; antiviral activity; antibacterial activity
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MDPI and ACS Style

Bereczki, I.; Papp, H.; Kuczmog, A.; Madai, M.; Nagy, V.; Agócs, A.; Batta, G.; Milánkovits, M.; Ostorházi, E.; Mitrović, A.; Kos, J.; Zsigmond, Á.; Hajdú, I.; Lőrincz, Z.; Bajusz, D.; Keserű, G.M.; Hodek, J.; Weber, J.; Jakab, F.; Herczegh, P.; Borbás, A. Natural Apocarotenoids and Their Synthetic Glycopeptide Conjugates Inhibit SARS-CoV-2 Replication. Pharmaceuticals 2021, 14, 1111. https://doi.org/10.3390/ph14111111

AMA Style

Bereczki I, Papp H, Kuczmog A, Madai M, Nagy V, Agócs A, Batta G, Milánkovits M, Ostorházi E, Mitrović A, Kos J, Zsigmond Á, Hajdú I, Lőrincz Z, Bajusz D, Keserű GM, Hodek J, Weber J, Jakab F, Herczegh P, Borbás A. Natural Apocarotenoids and Their Synthetic Glycopeptide Conjugates Inhibit SARS-CoV-2 Replication. Pharmaceuticals. 2021; 14(11):1111. https://doi.org/10.3390/ph14111111

Chicago/Turabian Style

Bereczki, Ilona, Henrietta Papp, Anett Kuczmog, Mónika Madai, Veronika Nagy, Attila Agócs, Gyula Batta, Márton Milánkovits, Eszter Ostorházi, Ana Mitrović, Janko Kos, Áron Zsigmond, István Hajdú, Zsolt Lőrincz, Dávid Bajusz, György M. Keserű, Jan Hodek, Jan Weber, Ferenc Jakab, Pál Herczegh, and Anikó Borbás. 2021. "Natural Apocarotenoids and Their Synthetic Glycopeptide Conjugates Inhibit SARS-CoV-2 Replication" Pharmaceuticals 14, no. 11: 1111. https://doi.org/10.3390/ph14111111

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