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Structure-based discovery of thiosemicarbazones as SARS-CoV-2 main protease inhibitors

The result's identifiers

  • Result code in IS VaVaI

    <a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F23%3A00574796" target="_blank" >RIV/61388963:_____/23:00574796 - isvavai.cz</a>

  • Result on the web

    <a href="https://doi.org/10.4155/fmc-2023-0034" target="_blank" >https://doi.org/10.4155/fmc-2023-0034</a>

  • DOI - Digital Object Identifier

    <a href="http://dx.doi.org/10.4155/fmc-2023-0034" target="_blank" >10.4155/fmc-2023-0034</a>

Alternative languages

  • Result language

    angličtina

  • Original language name

    Structure-based discovery of thiosemicarbazones as SARS-CoV-2 main protease inhibitors

  • Original language description

    Aim: Discovery of novel SARS-CoV-2 main protease (Mpro) inhibitors using a structure-based drug discovery strategy. Materials & methods: Virtual screening employing covalent and noncovalent docking was performed to discover Mpro inhibitors, which were subsequently evaluated in biochemical and cellular assays. Results: 91 virtual hits were selected for biochemical assays, and four were confirmed as reversible inhibitors of SARS CoV-2 Mpro with IC50 values of 0.4–3 μM. They were also shown to inhibit SARS-CoV-1 Mpro and human cathepsin L. Molecular dynamics simulations indicated the stability of the Mpro inhibitor complexes and the interaction of ligands at the subsites. Conclusion: This approach led to the discovery of novel thiosemicarbazones as potent SARS-CoV-2 Mpro inhibitors.

  • Czech name

  • Czech description

Classification

  • Type

    J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database

  • CEP classification

  • OECD FORD branch

    10608 - Biochemistry and molecular biology

Result continuities

  • Project

  • Continuities

    I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Others

  • Publication year

    2023

  • Confidentiality

    S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Data specific for result type

  • Name of the periodical

    Future Medicinal Chemistry

  • ISSN

    1756-8919

  • e-ISSN

    1756-8927

  • Volume of the periodical

    15

  • Issue of the periodical within the volume

    11

  • Country of publishing house

    GB - UNITED KINGDOM

  • Number of pages

    27

  • Pages from-to

    959-985

  • UT code for WoS article

    001024699400001

  • EID of the result in the Scopus database

    2-s2.0-85168222207