Recent Advances Towards Drug Design Targeting The Protease Of 2019 Novel Coronavirus (2019-Ncov)

CURRENT MEDICINAL CHEMISTRY(2021)

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摘要
Background: The 2019 novel coronavirus (2019-nCoV), also known as coronavirus 2 (SARS-CoV-2) acute respiratory syndrome has recently emerged and continued to spread rapidly with high mortality and morbidity rates. Currently, no efficacious therapy is available to relieve coronavirus infections. As new drug design and development takes time, there is a possibility offindingan effective treatment from existing antiviral agents. Objective: The aim of this study is to find out the relationship between thepossible drug targets and themechanism of action of antiviral drugs. This review discusses the efforts indevelopingdrug from known or new molecules. Methods: Viruses usually have two structural integrities, proteins and nucleic acids, both of which can be possible drug targets. Herein, we systemically discuss the structural -functional relationships of the spike, 3-chymotrypsin-like protease (3CLpro), papain like protease (PLpro) and RNA-dependent RNA polymerase (RdRp), as these are prominent structural features of thecoronavirus. Certain antiviral drugs such as Remdesivir are RNA-dependent RNA polymerase inhibitorswiththe ability to terminate RNA replication by inhibiting ATP. Results: It is reported that ATP is involved in synthesis of coronavirus non-structural proteins from 3CLpro and PLpro. Similarly, mechanisms of action of many other antiviral agents havebeen discussed in this review. It will provide new insights into the mechanism of inhibition, and let us develop new therapeutic antiviral approaches against novel SARS-CoV-2 coronavirus. Conclusion: In conclusion, this review summarizes recent progress in developing protease inhibitors for SARS-CoV-2.
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coronavirus, protease-like 3-chymotrypsin (3CLpro), protease-like papain (PLpro), remdesivir, SARS-CoV-2, non-structural proteins, ATP
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