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

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.