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...

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Autores principales:	Ilona Bereczki, 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 Miklós Keserű, Jan Hodek, Jan Weber, Ferenc Jakab, Pál Herczegh, Anikó Borbás
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	teicoplanin ristocetin bixin crocetin β-apocarotenoic acid SARS-CoV-2 Medicine R Pharmacy and materia medica RS1-441
Acceso en línea:	https://doaj.org/article/f24dbbab6dc04e6c8e451af15f46c4d7
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spelling	oai:doaj.org-article:f24dbbab6dc04e6c8e451af15f46c4d72021-11-25T18:39:26ZNatural Apocarotenoids and Their Synthetic Glycopeptide Conjugates Inhibit SARS-CoV-2 Replication10.3390/ph141111111424-8247https://doaj.org/article/f24dbbab6dc04e6c8e451af15f46c4d72021-10-01T00:00:00Zhttps://www.mdpi.com/1424-8247/14/11/1111https://doaj.org/toc/1424-8247The 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.Ilona BereczkiHenrietta PappAnett KuczmogMónika MadaiVeronika NagyAttila AgócsGyula BattaMárton MilánkovitsEszter OstorháziAna MitrovićJanko KosÁron ZsigmondIstván HajdúZsolt LőrinczDávid BajuszGyörgy Miklós KeserűJan HodekJan WeberFerenc JakabPál HerczeghAnikó BorbásMDPI AGarticleteicoplaninristocetinbixincrocetinβ-apocarotenoic acidSARS-CoV-2MedicineRPharmacy and materia medicaRS1-441ENPharmaceuticals, Vol 14, Iss 1111, p 1111 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	teicoplanin ristocetin bixin crocetin β-apocarotenoic acid SARS-CoV-2 Medicine R Pharmacy and materia medica RS1-441
spellingShingle	teicoplanin ristocetin bixin crocetin β-apocarotenoic acid SARS-CoV-2 Medicine R Pharmacy and materia medica RS1-441 Ilona Bereczki 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 Miklós Keserű Jan Hodek Jan Weber Ferenc Jakab Pál Herczegh Anikó Borbás Natural Apocarotenoids and Their Synthetic Glycopeptide Conjugates Inhibit SARS-CoV-2 Replication
description	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.
format	article
author	Ilona Bereczki 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 Miklós Keserű Jan Hodek Jan Weber Ferenc Jakab Pál Herczegh Anikó Borbás
author_facet	Ilona Bereczki 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 Miklós Keserű Jan Hodek Jan Weber Ferenc Jakab Pál Herczegh Anikó Borbás
author_sort	Ilona Bereczki
title	Natural Apocarotenoids and Their Synthetic Glycopeptide Conjugates Inhibit SARS-CoV-2 Replication
title_short	Natural Apocarotenoids and Their Synthetic Glycopeptide Conjugates Inhibit SARS-CoV-2 Replication
title_full	Natural Apocarotenoids and Their Synthetic Glycopeptide Conjugates Inhibit SARS-CoV-2 Replication
title_fullStr	Natural Apocarotenoids and Their Synthetic Glycopeptide Conjugates Inhibit SARS-CoV-2 Replication
title_full_unstemmed	Natural Apocarotenoids and Their Synthetic Glycopeptide Conjugates Inhibit SARS-CoV-2 Replication
title_sort	natural apocarotenoids and their synthetic glycopeptide conjugates inhibit sars-cov-2 replication
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/f24dbbab6dc04e6c8e451af15f46c4d7
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Natural Apocarotenoids and Their Synthetic Glycopeptide Conjugates Inhibit SARS-CoV-2 Replication

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