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

Immun Inflamm Dis. 2022 Jan;10(1):22-25. doi: 10.1002/iid3.549. Epub 2021 Oct 13.

Abstract

Background: The lack of knowledge about the specific preventive measures and limited scientific information on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to an excruciating onset and progression of coronavirus disease 2019 (COVID-19). Swift development of various successful vaccines around the globe is striving to contain the exponential surges of COVID-19 cases. However, the ongoing struggle to vaccinate the global population and alarming spread of highly transmissible variants may thwart global initiatives to contain SARS-CoV-2 as observed by less robust protective immunity.

Methods: In this perspective, we propose a thought-provoking, two-pronged strategy involving RNA interference approach to degrade essential SARS-CoV-2 ORFs required for replication and entry in conjunction with a complement inhibitor (compstatin) to stymie the detrimental proinflammatory cytokine storm that exacerbate disease progression and severity.

Results: We provide supporting evidence suggesting that concurrent targeting of viral and host components will be a superior strategy to effectively suppress viral spread and clinical manifestations of COVID-19.

Conclusion: SARS-CoV-2 specific RNAi in conjunction with systemic delivery of compstatin will be an effective two-pronged strategy to combat local and systemic immune responses in both symptomatic and asymptomatic COVID-19 patients.

Keywords: complement; gene regulation processes; infections; molecules; viral/retroviral.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • COVID-19 Drug Treatment*
  • Complement Inactivating Agents / therapeutic use*
  • Complement System Proteins
  • Cytokines
  • Humans
  • RNA Interference*

Substances

  • Complement Inactivating Agents
  • Cytokines
  • Complement System Proteins