Grant: Operating Grant: COVID-19 Rapid Research Funding Opportunity - Therapeutics

The cataclysmic threat that viruses pose for human health and predicted by virologists for decades has been made crystal clear by the current COVID-19 pandemic. A huge success in curtailing viral infections has been the development of safe and potent vaccines that confer extended immunity as well as the development of antiviral drugs. Many viruses however evolve rapidly (e.g., influenza A, coronaviruses, etc.) rendering previous vaccinations ineffective and drugs obsolete. We propose the development of a new platform that will convert defective particles, generated by all viruses during infection, into antiviral therapies. Defective Interfering particles (DIs) arise during the propagation and spread of a virus infection and are generated by errors made during viral replication. DIs cannot replicate in the absence of the parental virus due to a lack of essential genes, making them "parasites" of the parental virus. Hence, if a DI enters an uninfected cell, there is no infectious virus produced and no deleterious effects on that cell. However, their presence in an infected cell has a profound effect on the replication of wild-type virus since they compete for limiting cellular resources during an infection, thus leading to reduced viral yields and blunting of the infection. Many DIs are also able to induce an antiviral response. There is no published information on the type of DIs that arise during a SARS-CoV-2 infection and how these might impact COVID-19 disease progression - a knowledge gap that these studies will address. In parallel to studies aimed at better understanding COVID-19 disease modifiers, we will also engineer DIs to generate INTERCEPTORs - a new anti-viral therapeutic for the treatment of COVID-19. INTERCEPTORs will be designed from DIs to halt an ongoing infection in progress and significantly decrease disease pathology.