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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.
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.
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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