Grant: Project Grant - PA: Infection and Immunity (Early Career Research Support)

Coronavirus disease-19 (Covid-19) pandemic is the biggest global health crisis in recent history, resulting in over 4.5 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. The virus has spread to nearly all communities across the globe, leading to hospitalizations and deaths. Highly transmissible virus variants are now regularly 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 accompanied by genetic 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 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 mutations in SARS-Coronavirus-2 genome led to emergence of highly virulent and fast spreading delta variant. Understanding the mechanisms behind increased virulence of delta variant is critical, for effective disease management, development of vaccines and therapeutics and to rapidly respond to the emergence of new variants in future. 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 this study, we will examine several previously unexplored aspects of the virus biology and identify novel targets for development of effective antivirals.