SARS-CoV-2 targeting by RNAi and host complement inhibition: A two-pronged subterfuge for COVID-19 treatment

Raza Ali Naqvi1, Deepak Shukla2,3, Afsar R Naqvi1

  • 1Department of Periodontics, College of Dentistry, University of Illinois at Chicago, Chicago, Illinois, USA.

Abstract

Insights

A novel two-pronged strategy combining RNA interference (RNAi) and a complement inhibitor (compstatin) offers a promising approach to combat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This method targets both viral replication and the inflammatory cytokine storm in COVID-19 patients.

Area of Science:

  • Virology
  • Immunology
  • Molecular Biology

Background:

  • Limited understanding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its prevention led to severe coronavirus disease 2019 (COVID-19) outcomes.
  • While vaccines have been developed, challenges in global vaccination and the emergence of variants with robust transmissibility hinder containment efforts.
  • Less robust protective immunity against SARS-CoV-2 underscores the need for novel therapeutic strategies.

Purpose of the Study:

  • To propose a dual-action therapeutic strategy against SARS-CoV-2.
  • To address both viral proliferation and the severe inflammatory response in COVID-19.

Main Methods:

  • Utilizing RNA interference (RNAi) to degrade essential SARS-CoV-2 open reading frames (ORFs) crucial for viral replication and entry.
  • Employing a complement inhibitor, specifically compstatin, to mitigate the cytokine storm associated with severe COVID-19.

Main Results:

  • Concurrent targeting of both viral and host factors is presented as a superior approach.
  • Evidence suggests this combined strategy can effectively suppress viral spread and clinical symptoms of COVID-19.

Conclusions:

  • A two-pronged strategy involving SARS-CoV-2-specific RNAi and systemic compstatin delivery is proposed.
  • This approach is anticipated to be effective in managing both local and systemic immune responses in symptomatic and asymptomatic COVID-19 patients.

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