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Advances in developing ACE2 derivatives against SARS-CoV-2.

Haoran Zhang1, Panjing Lv1, Jingrui Jiang1

  • 1Department of Pathogen Biology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, China.

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New ACE2 derivatives show potent neutralization against SARS-CoV-2 variants, offering improved efficacy and bioavailability over traditional antibodies for COVID-19 treatment.

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Area of Science:

  • Virology
  • Immunology
  • Biotechnology

Background:

  • SARS-CoV-2 variants exhibit extensive immune evasion, diminishing the effectiveness of existing therapeutic antibodies.
  • Despite mutations, variants retain binding to human angiotensin-converting enzyme 2 (ACE2) via the spike protein, presenting a vulnerability.

Purpose of the Study:

  • To review recent advancements (past 3 years) in developing ACE2 derivatives as potential therapeutics against SARS-CoV-2.
  • To assess the efficacy, production, and bioavailability of these novel ACE2-based inhibitors.

Main Methods:

  • Review of literature on recombinant ACE2 proteins, ACE2-loaded extracellular vesicles, ACE2-mimicking antibodies, and peptide/mini-protein mimetics.
  • Analysis of auxiliary techniques like chemical modification and recombinant design enhancing derivative performance.

Main Results:

  • ACE2 derivatives demonstrate potent neutralization of SARS-CoV-2 variants, often exceeding endogenous antibody capabilities.
  • These derivatives exhibit enhanced production efficiency and improved bioavailability.
  • Various strategies have been employed to optimize ACE2 derivative design and function.

Conclusions:

  • ACE2 derivatives represent a promising therapeutic strategy against immune-evasive SARS-CoV-2 variants.
  • Further development of these ACE2-based decoys is expected to yield effective COVID-19 treatments.
  • The findings highlight the potential of mimicking host-pathogen interactions for therapeutic intervention.