SARS-CoV Adaptations Through a Systems Biology Lens

Since the onset of the pandemic, SARS-CoV-2 has infected over 290 million people and caused 5.5 million deaths, with the virus continuously evolving into more transmissible variants. The central underlying hypothesis of SYBIL is that host genes and networks involved in viral replication and in early host responses regulate disease outcome and represent promising targets for therapeutic intervention. The program leverages an integrated systems level approach to discover and characterize the critical networks involved in SARS-CoV replication, host adaptation, pathogenesis, their associated biomarkers, and key drivers of these signatures that can be targeted for therapeutic intervention.

 

SYBIL is the renewal and a logical extension of our previous consortium entitled “FluOMICS: The Next Generation”. The FluOMICS program characterized the impact of influenza virus infection on the global epigenome, transcriptome, proteome and metabolome in primary relevant human cells and in human and mouse tissues after infection with influenza viruses, resulting in diverse outcomes of disease severity. After the onset of the COVID-19 pandemic, the program applied the FluOMICS systems biology/modeling research platform to characterize networks associated with SARS-CoV-2 infections that regulate virus replication and disease, leading to targeted interventions now being tested in clinical trials for COVID-19. The SYBIL project continues this trajectory, aiming to deepen our understanding of virus-host interactions, enhance therapeutic strategies, and explore factors that facilitate zoonotic transmission and human adaptation. The project not only seeks to manage the COVID-19 pandemic but also to improve responses to future viral outbreaks.