Grant: Project Grant - PA: Pandemic and Health Emergencies Research

Coronavirus disease-19 (Covid-19) pandemic is the biggest global health crisis in recent history, resulting in over 2.7 million deaths worldwide. Covid-19 is caused by SARS-Coronavirus-2, a novel coronavirus that was unknown until human infections were first reported from China in late 2019. Over the last year, the virus has spread across all communities across the globe leading to hospitalizations and deaths. Highly transmissible virus variants are now regularily emerging and spreading among populations in several countries exacerbating the current crisis. To date, there are no effective antivirals to combat the disease and the evolution of new virus variants is threatening the efficacy of available vaccines. The emergence of highly infectious virus variants was always accompanied by genetics changes of viral proteins, which have roles in virus entry, neutralizing host antiviral defenses and exploiting cellular pathways during infection. Several new genes were also discovered recently in SARS-Coronavirus-2 genome which may likely have roles in virus fitness and pathogenesis. We have been exploring the interactions between SARS-Coronavirus-2 and the host cells over the last year and have identified multiple cellular pathways playing critical functions during infection. With the present study, we aim to investigate how changes in SARS-Coronavirus-2 genome led to higher virulence of fast spreading virus variants. Understanding the mechanisms behind increased virulence of variants is critical, for effective disease management and development of vaccines and therapeutics. We will also explore the roles of proteins encoded by novel genes in infection and virus spread, to better understand the biology of SARS-Coronavirus-2. During the course of this study, we will examine several previously unexplored aspects of the virus biology and identify novel targets for development of effective antivirals.