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

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.