ABSTRACT
To date, a total of seven human coronaviruses (HCoVs) have been identified, all of which are important respiratory pathogens. Recently, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has led to a global pandemic causing millions of infections and deaths. Here, we summarize the discovery and fundamental virology of HCoVs, discuss their zoonotic transmission and highlight the weak species barrier of SARS-CoV-2. We also discuss the possible origins of SARS-CoV-2 variants of concern identified to date and discuss the experimental challenges in characterizing mutations of interest and propose methods to circumvent them. As the COVID-19 treatment and prevention landscape rapidly evolves, we summarize current therapeutics and vaccines, and their implications on SARS-CoV-2 variants. Finally, we explore how interspecies transmission of SARS-CoV-2 may drive the emergence of novel strains, how disease severity may evolve and how COVID-19 will likely continue to burden healthcare systems globally.