Number of the records: 1  

Rational Design of Highly Potent SARS-CoV-2 nsp14 Methyltransferase Inhibitors

  1. 1.
    SYSNO ASEP0574244
    Document TypeJ - Journal Article
    R&D Document TypeJournal Article
    Subsidiary JČlánek ve WOS
    TitleRational Design of Highly Potent SARS-CoV-2 nsp14 Methyltransferase Inhibitors
    Author(s) Štefek, Milan (UOCHB-X)
    Chalupská, Dominika (UOCHB-X) ORCID
    Chalupský, Karel (UOCHB-X)
    Zgarbová, Michala (UOCHB-X)
    Dvořáková, Alexandra (UOCHB-X)
    Krafčíková, Petra (UOCHB-X) ORCID
    Li, A. S. M. (CA)
    Šála, Michal (UOCHB-X) RID, ORCID
    Dejmek, Milan (UOCHB-X) RID, ORCID
    Otava, Tomáš (UOCHB-X) ORCID
    Chaloupecká, Ema (UOCHB-X) ORCID
    Kozák, Jaroslav (UOCHB-X) RID, ORCID
    Kozic, Ján (UOCHB-X) ORCID
    Vedadi, M. (CA)
    Weber, Jan (UOCHB-X) RID, ORCID
    Mertlíková-Kaiserová, Helena (UOCHB-X) RID, ORCID
    Nencka, Radim (UOCHB-X) RID, ORCID
    Source TitleACS Omega. - : American Chemical Society - ISSN 2470-1343
    Roč. 8, č. 30 (2023), s. 27410-27418
    Number of pages9 s.
    Languageeng - English
    CountryUS - United States
    KeywordsSARS-CoV-2 ; genetics ; inhibitors
    OECD categoryVirology
    R&D ProjectsNU20-05-00472 GA MZd - Ministry of Health (MZ)
    LX22NPO5103 GA MŠMT - Ministry of Education, Youth and Sports (MEYS)
    Method of publishingOpen access
    Institutional supportUOCHB-X - RVO:61388963
    UT WOS001031748300001
    EID SCOPUS85166762149
    DOI10.1021/acsomega.3c02815
    AnnotationThe search for new drugs against COVID-19 and its causative agent, SARS-CoV-2, is one of the major trends in the current medicinal chemistry. Targeting capping machinery could be one of the therapeutic concepts based on a unique mechanism of action. Viral RNA cap synthesis involves two methylation steps, the first of which is mediated by the nsp14 protein. Here, we rationally designed and synthesized a series of compounds capable of binding to both the S-adenosyl-l-methionine and the RNA-binding site of SARS-CoV-2 nsp14 N7-methyltransferase. These hybrid molecules showed excellent potency, high selectivity toward various human methyltransferases, nontoxicity, and high cell permeability. Despite the outstanding activity against the enzyme, our compounds showed poor antiviral performance in vitro. This suggests that the activity of this viral methyltransferase has no significant effect on virus transcription and replication at the cellular level. Therefore, our compounds represent unique tools to further explore the role of the SARS-CoV-2 nsp14 methyltransferase in the viral life cycle and the pathogenesis of COVID-19.
    WorkplaceInstitute of Organic Chemistry and Biochemistry
    Contactasep@uochb.cas.cz ; Kateřina Šperková, Tel.: 232 002 584 ; Jana Procházková, Tel.: 220 183 418
    Year of Publishing2024
    Electronic addresshttps://doi.org/10.1021/acsomega.3c02815
Number of the records: 1  

  This site uses cookies to make them easier to browse. Learn more about how we use cookies.