These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Rational Design of Highly Potent SARS-CoV-2 nsp14 Methyltransferase Inhibitors.
    Author: Štefek M, Chalupská D, Chalupský K, Zgarbová M, Dvořáková A, Krafčíková P, Li ASM, Šála M, Dejmek M, Otava T, Chaloupecká E, Kozák J, Kozic J, Vedadi M, Weber J, Mertlíková-Kaiserová H, Nencka R.
    Journal: ACS Omega; 2023 Aug 01; 8(30):27410-27418. PubMed ID: 37546609.
    Abstract:
    The 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.
    [Abstract] [Full Text] [Related] [New Search]