Genetic and epigenetic diversity of protein molecules related to SARS-CoV-2 entry: where we are and where we should go Running title: Genetic and epigenetic diversity of protein molecules related to SARS-CoV-2 entry

Abstract: The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), has swept the whole world and brought about public health crisis of unprecedented proportions. In the process of SARS-CoV-2 entry, angiotensin-converting enzyme 2 plays a key role. In addition, other protein molecules such as transmembrane protease/serine 2, FURIN, Cathepsin L, and a disintegrin and metalloproteinase 17 will also affect the interaction between virus and host cells. Since the variations in the virus and human populations could determine transmissibility of the virus and influence an individual’s susceptibility to SARS-CoV-2 infection and disease outcome, research on the variations of above protein molecules and their role in COVID-19 is in full swing. In this review, we systematically reviewed viral and host genetic variations related to SARS-CoV-2 entry, as well as the relationship between the diversity of these variations and COVID-19 pandemic. We aim to provide better insights into the transmission and pathogenesis of COVID-19 from the perspective of genetic variants and epigenetic factors, so as to prevent, control, and treat COVID-19, especially among high-risk populations with genetic risk variants.