The Structure-Based Design of SARS-CoV-2 nsp14 Methyltransferase Ligands Yields Nanomolar Inhibitors
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F21%3A00544555" target="_blank" >RIV/61388963:_____/21:00544555 - isvavai.cz</a>
Result on the web
<a href="https://doi.org/10.1021/acsinfecdis.1c00131" target="_blank" >https://doi.org/10.1021/acsinfecdis.1c00131</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1021/acsinfecdis.1c00131" target="_blank" >10.1021/acsinfecdis.1c00131</a>
Alternative languages
Result language
angličtina
Original language name
The Structure-Based Design of SARS-CoV-2 nsp14 Methyltransferase Ligands Yields Nanomolar Inhibitors
Original language description
In this study, we have focused on the structure-based design of the inhibitors of one of the two SARS-CoV-2 methyltransferases (MTases), nsp14. This MTase catalyzes the transfer of the methyl group from S-adenosyl-l-methionine (SAM) to cap the guanosine triphosphate moiety of the newly synthesized viral RNA, yielding the methylated capped RNA and S-adenosyl-l-homocysteine (SAH). As the crystal structure of SARS-CoV-2 nsp14 is unknown, we have taken advantage of its high homology to SARS-CoV nsp14 and prepared its homology model, which has allowed us to identify novel SAH derivatives modified at the adenine nucleobase as inhibitors of this important viral target. We have synthesized and tested the designed compounds in vitro and shown that these derivatives exert unprecedented inhibitory activity against this crucial enzyme. The docking studies nicely explain the contribution of an aromatic part attached by a linker to the position 7 of the 7-deaza analogues of SAH.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10606 - Microbiology
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2021
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
ACS Infectious Diseases
ISSN
2373-8227
e-ISSN
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Volume of the periodical
7
Issue of the periodical within the volume
8
Country of publishing house
US - UNITED STATES
Number of pages
7
Pages from-to
2214-2220
UT code for WoS article
000685949500021
EID of the result in the Scopus database
2-s2.0-85110951126