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Research progress on critical viral protease inhibitors for coronaviruses and enteroviruses

Shulei Hu1, Qiuyu Zhong1, Xiong Xie2

  • 1China Pharmaceutical University, 639 Longmian Avenue, Jiangning District, Nanjing 211198, China; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, China.

Bioorganic & Medicinal Chemistry Letters
|March 12, 2025
PubMed

Insights

This review explores viral proteases from SARS-CoV-2 and Enterovirus 71 (EV71), focusing on their roles in immune evasion and potential as drug targets. Understanding these viral proteases is key for developing new antiviral therapies against infectious diseases.

Area of Science:

  • Virology
  • Immunology
  • Drug Discovery

Background:

  • Viral infectious diseases pose significant global health challenges.
  • Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) causes COVID-19, while Enterovirus 71 (EV71) is a primary cause of Hand, Foot, and Mouth Disease (HFMD).
  • Effective direct-acting antiviral drugs are lacking for EV71, and understanding viral mechanisms is crucial for developing new treatments.

Purpose of the Study:

  • To review the current understanding of key viral proteases: SARS-CoV-2 3CLpro and PLpro, and EV71 3Cpro and 2Apro.
  • To analyze the structure, function, and immune modulation activities of these viral proteases.
  • To explore existing and potential inhibitors for these proteases, offering insights for drug development.

Main Methods:

  • Literature review of scientific publications on viral proteases.
  • Analysis of protease structures and functions.
  • Examination of studies on protease-mediated modulation of host innate immunity.
  • Survey of identified inhibitors targeting these viral proteases.

Main Results:

  • Viral proteases play critical roles in viral replication and pathogenesis by cleaving polyproteins.
  • These proteases can actively modulate host innate immune responses to facilitate viral proliferation.
  • Structural and functional data are available for SARS-CoV-2 and EV71 proteases, with some inhibitors identified.

Conclusions:

  • Viral proteases are essential for viral survival and represent promising targets for antiviral drug development.
  • Targeting SARS-CoV-2 3CLpro, PLpro, and EV71 3Cpro/2Apro offers a potential strategy to combat COVID-19 and HFMD.
  • Further research into protease inhibitors could lead to novel therapeutic interventions against these viral infections.
Keywords:
2A(pro)EV71 3C(pro)Innate immunity responsePL(pro)SARS-CoV-2 3CL(pro)Viral protease inhibitor

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