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PubMed Central
Other literature type . 2022
Data sources: PubMed Central
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European Journal of Medicinal Chemistry
Article . 2022 . Peer-reviewed
License: Elsevier TDM
Data sources: Crossref
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Design, synthesis and in vitro evaluation of novel SARS-CoV-2 3CLpro covalent inhibitors

Authors: Julia K. Stille; Jevgenijs Tjutrins; Guanyu Wang; Felipe A. Venegas; Christopher Hennecker; Andrés M. Rueda; Itai Sharon; +13 Authors

Design, synthesis and in vitro evaluation of novel SARS-CoV-2 3CLpro covalent inhibitors

Abstract

Severe diseases such as the ongoing COVID-19 pandemic, as well as the previous SARS and MERS outbreaks, are the result of coronavirus infections and have demonstrated the urgent need for antiviral drugs to combat these deadly viruses. Due to its essential role in viral replication and function, 3CLpro (main coronaviruses cysteine-protease) has been identified as a promising target for the development of antiviral drugs. Previously reported SARS-CoV 3CLpro non-covalent inhibitors were used as a starting point for the development of covalent inhibitors of SARS-CoV-2 3CLpro. We report herein our efforts in the design and synthesis of submicromolar covalent inhibitors when the enzymatic activity of the viral protease was used as a screening platform.

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Keywords

Drug Design, Animals, Humans, Protease Inhibitors, Virus Replication, Antiviral Agents, Article, Coronavirus 3C Proteases, High-Throughput Screening Assays, COVID-19 Drug Treatment

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    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    68
    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 1%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    Top 10%
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 1%
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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
68
Top 1%
Top 10%
Top 1%
Green
bronze