Host-pathogen interactions in the context of coronaviruses

While the COVID-19 pandemic is largely behind us, it continues to kill people (7 million so far) and has had a lasting impact on the world economy. While SARS-CoV-2, the causative agent for COVID-19, is a dangerous human pathogen, other viruses of the same family (called coronaviruses) have also been highly problematic (SARS-CoV in 2002, MERS-CoV in 2012) and may again be an issue in the future. Meanwhile, although most people ignore it, several endemic human coronaviruses have been around for decades and causing mild cold symptoms. This is an unique opportunity to understand what distinguishes these different coronaviruses to better control them. Moreover, as viruses depend on our own proteins to propagate, knowing which cellular proteins are needed by the viruses is critical and a useful way to target them by novel therapeutic approaches. Our laboratory specializes in the analysis of host-pathogen interactions and has spent much of the last two decades deciphering how another human pathogen (herpes simplex virus type 1, which can induce a variety of mild to severe diseases) interacts with our cells. More specifically, our approach has been to identify the cellular proteins that are packaged inside the mature viruses and examine their role at the molecular level. We are now applying this knowhow to characterize the interactions between our cells and two coronaviruses, HCoV-OC43 (a milder coronavirus) and SARS-CoV-2 (an aggressive coronavirus). As the latter is rapidly evolving, we are also probing variants of SARS-CoV-2 that arose with time (original Wuhan-HU-1 virus and Delta/Omicron variants). This will inform us on what these viruses specifically need from our cells, enable us to probe how certain host proteins may drive their virulence and provide new molecular targets.