Počet záznamů: 1
Potent Anti-SARS-CoV-2 Activity by the Natural Product Gallinamide A and Analogues via Inhibition of Cathepsin L
- 1.
SYSNO ASEP 0558333 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Potent Anti-SARS-CoV-2 Activity by the Natural Product Gallinamide A and Analogues via Inhibition of Cathepsin L Tvůrce(i) Ashhurst, A. S. (AU)
Tang, A. H. (AU)
Fajtová, Pavla (UOCHB-X) RID, ORCID
Yoon, M. C. (US)
Aggarwal, A. (AU)
Bedding, M. J. (AU)
Stoye, A. (AU)
Beretta, L. (US)
Pwee, D. (US)
Drelich, A. (US)
Skinner, D. (US)
Li, L. (US)
Meek, T. D. (US)
McKerrow, J. H. (US)
Hook, V. (US)
Tseng, C. T. (US)
Larance, M. (AU)
Turville, S. (AU)
Gerwick, W. H. (US)
O'Donoghue, A. J. (US)
Payne, R. J. (AU)Zdroj.dok. Journal of Medicinal Chemistry. - : American Chemical Society - ISSN 0022-2623
Roč. 65, č. 4 (2022), s. 2956-2970Poč.str. 15 s. Jazyk dok. eng - angličtina Země vyd. US - Spojené státy americké Klíč. slova acute respiratory syndrome ; cell entry ; selective inhibitor Obor OECD Biochemistry and molecular biology Způsob publikování Open access Institucionální podpora UOCHB-X - RVO:61388963 UT WOS 000797940600016 EID SCOPUS 85119036179 DOI 10.1021/acs.jmedchem.1c01494 Anotace Cathepsin L is a key host cysteine protease utilized by coronaviruses for cell entry and is a promising drug target for novel antivirals against SARS-CoV-2. The marine natural product gallinamide A and several synthetic analogues were identified as potent inhibitors of cathepsin L with IC50 values in the picomolar range. Lead molecules possessed selectivity over other cathepsins and alternative host proteases involved in viral entry. Gallinamide A directly interacted with cathepsin L in cells and, together with two lead analogues, potently inhibited SARS-CoV-2 infection in vitro, with EC50 values in the nanomolar range. Reduced antiviral activity was observed in cells overexpressing transmembrane protease, serine 2 (TMPRSS2), however, a synergistic improvement in antiviral activity was achieved when combined with a TMPRSS2 inhibitor. These data highlight the potential of cathepsin L as a COVID-19 drug target as well as the likely need to inhibit multiple routes of viral entry to achieve efficacy. Pracoviště Ústav organické chemie a biochemie Kontakt asep@uochb.cas.cz ; Kateřina Šperková, Tel.: 232 002 584 ; Viktorie Chládková, Tel.: 232 002 434 Rok sběru 2023 Elektronická adresa https://doi.org/10.1021/acs.jmedchem.1c01494
Počet záznamů: 1