Project 465304

Betacoronavirus (beta-CoV) is one of four genera of coronaviruses (CoVs) that includes severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and Middle East respiratory syndrome coronavirus (MERS-CoV). MERS-CoV evolved in 2012 and continues to cause seasonal outbreaks in the Kingdom of Saudi Arabia (KSA), along with travel-related cases. MERS-CoV is listed by the World Health Organization (WHO) as a pandemic threat. SARS-CoV-2 emerged in December 2019 and has caused a global pandemic. MERS-CoV has a higher fatality rate compared to SARS-CoV-2. Despite epidemiological data suggesting a higher death rate for MERS-CoV infections compared to SARS-CoV-2, little is known about why MERS-CoV infections can be more lethal. CoV accessory proteins are dispensable for virus replication, but these proteins play an important role in blocking human antiviral responses, thus allowing the viruses to replicate with limited resistance from infected human cells. We hypothesize that MERS-CoV accessory proteins are more efficient in blocking human antiviral responses compared to SARS-CoV-2, which contributes to increased disease severity and mortality on infection with MERS-CoV. During this 5-year study, we will identify differences in molecular markers of disease on infection with MERS-CoV and SARS-CoV-2. We will specifically focus on MERS-CoV and SARS-CoV-2 accessory proteins and identify regions within these proteins that are directly responsible for subverting human antiviral responses. Our studies will discover the potential of MERS-CoV and SARS-CoV-2 accessory proteins to block human antiviral responses and inform the development of novel pan-coronavirus drugs to combat the ongoing pandemic and mitigate risks from future emerging beta-CoV outbreaks.