Overall, we speculate that the reason why COVID-19 has become a once-in-a-century pandemic while SARS ended up with epidemics in the past could be, at least in part, that the S protein, a key viral protein for the first step in transmission, of the causative agent SARS-CoV-2, displays suboptimal levels of cell entry activity as shown in this study. The gene discussed is PROS1; the disease is COVID-19.