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Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside...
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During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA.  Marilyn Kozak discovered that the sequence RCCAUGG (where R...
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A Fluorogenic Peptide Cleavage Assay to Screen for Proteolytic Activity: Applications for coronavirus spike protein activation
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SARS-CoV-2 Papain-Like Protease: Structure, Function and Inhibition.

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  • 1Research School of Chemistry, Australian National University, Canberra, ACT 2601, Australia.

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Summary

Investigating the SARS-CoV-2 papain-like protease (PLpro) is crucial for developing new antiviral drugs. This review details PLpro

Keywords:
COVID-19antiviralsimmune responseposttranslational modificationsprotease inhibitors

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Area of Science:

  • Virology
  • Drug Discovery
  • Molecular Biology

Background:

  • Emerging SARS-CoV-2 variants and novel coronaviruses necessitate identification of new drug targets.
  • The coronavirus papain-like protease (PLpro) plays a key role in viral replication and immune modulation, making it a promising therapeutic target.
  • PLpro remains less explored compared to other viral proteins.

Purpose of the Study:

  • To review the structure and function of SARS-CoV-2 PLpro.
  • To compare SARS-CoV-2 PLpro with homologous proteases from SARS-CoV-1 and MERS-CoV.
  • To discuss potential inhibitors and their therapeutic prospects.

Main Methods:

  • Literature review of existing research on coronavirus PLpro.
  • Structural and functional analysis of SARS-CoV-2 PLpro.
  • Comparative analysis of PLpro across different coronaviruses.

Main Results:

  • SARS-CoV-2 PLpro shares structural and functional similarities with other coronavirus PLpro enzymes.
  • The protease's recognition motif is conserved in host proteins like ubiquitin and ISG15, crucial for antiviral immunity.
  • Inhibitors such as GRL0617 derivatives show potential for therapeutic intervention.

Conclusions:

  • SARS-CoV-2 PLpro is a validated target for antiviral drug development.
  • Understanding PLpro's interaction with host immune factors is key to designing effective inhibitors.
  • Further research into PLpro inhibitors could lead to novel treatments against SARS-CoV-2 and other coronaviruses.