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Structural insights of key enzymes into therapeutic intervention against SARS-CoV-2

Munazza Shahid1, Syed Shahzad-Ul-Hussan1

  • 1Department of Biology, SBA School of Science and Engineering, Lahore University of Management Sciences, Lahore 54792, Pakistan.

Journal of Structural Biology
|December 31, 2020
PubMed

Insights

This review details key SARS-CoV-2 proteins and host factors, identifying potential therapeutic targets for COVID-19 drug discovery. Structural insights into viral enzymes and host interactions guide rational drug design against the pandemic virus.

Area of Science:

  • Virology and Drug Discovery
  • Structural Biology
  • Infectious Diseases

Background:

  • The COVID-19 pandemic, caused by SARS-CoV-2, necessitates rapid therapeutic strategies.
  • Drug repurposing has been a primary approach, but specific treatments remain elusive.
  • Emerging structural data on SARS-CoV-2 proteins and host factors offers new avenues for drug development.

Purpose of the Study:

  • To review the structural details of key SARS-CoV-2 viral enzymes and host factors.
  • To identify potential therapeutic intervention sites (hotspots) on these structures.
  • To discuss the significance of endoplasmic reticulum α-glucosidases as drug targets.

Main Methods:

  • Recapitulation of structural data for SARS-CoV-2 RNA-dependent RNA polymerase, 3-chymotrypsin-like protease, papain-like protease, and helicase.
  • Analysis of structural information for host factors angiotensin-converting enzyme 2 and transmembrane serine protease.
  • Review of literature on endoplasmic reticulum α-glucosidases in the context of SARS-CoV-2 infection.

Main Results:

  • Detailed structural descriptions of critical viral enzymes and host interaction proteins.
  • Identification of potential 'hotspots' on these structures for targeted drug design.
  • Highlighting endoplasmic reticulum α-glucosidases as promising targets for novel antiviral therapies.

Conclusions:

  • Structural biology provides a foundation for rational drug design against SARS-CoV-2.
  • Targeting specific viral enzymes and host factors, including ER α-glucosidases, offers therapeutic potential.
  • Further exploration of identified hotspots could lead to effective COVID-19 treatments.
Keywords:
3CLproCOVID-19PolymeraseSARS-CoV-2Therapeutic targetsα-Glucosidase inhibitor

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