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

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

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.

• Jezik: Angleški jezik
• Ključne besede: teicoplanin, ristocetin, bixin, crocetin, β-apocarotenoic acid, SARS-CoV-2, antiviral activity, antibacterial activity
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: FFA - Fakulteta za farmacijo
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2021
• Št. strani: 25 str.
• Številčenje: Vol. 14, iss. 11, art. 1111
• PID: 20.500.12556/RUL-136426
• UDK: 577
• ISSN pri članku: 1424-8247
• DOI: 10.3390/ph14111111
• COBISS.SI-ID: 83004931
• Datum objave v RUL: 03.05.2022

Gradivo je del revije

• Naslov: Pharmaceuticals
• Skrajšan naslov: Pharmaceuticals
• Založnik: MDPI
• ISSN: 1424-8247
• COBISS.SI-ID: 517582617

Licence

• Licenca: CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by/4.0/deed.sl
• Opis: To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.
• Začetek licenciranja: 01.11.2021