Coronavirus entry: how we arrived at SARS-CoV-2

Abstract

Because of the COVID-19 pandemic, the novel coronavirus SARS-CoV-2 has risen to shape scientific research during 2020, with its spike (S) protein being a predominant focus. The S protein is likely the most complicated of all viral glycoproteins and is a key factor in immunological responses and virus pathogenesis. It is also the driving force dictating virus entry mechanisms, which are highly 'plastic' for coronaviruses, allowing a plethora of options for different virus variants and strains in different cell types. Here we review coronavirus entry as a foundation for current work on SARS-CoV-2. We focus on the post-receptor binding events and cellular pathways that direct the membrane fusion events necessary for genome delivery, including S proteolytic priming and activation. We also address aspects of the entry process important for virus evolution and therapeutic development.

Figure 1

A coronavirus entry triad. Coronavirus host cell entry is determined by a triad of factors: receptor binding and protease cleavage work in concert with the ionic environment of the cell/subcellular compartment to facilitate membrane fusion. Coronavirus spike proteins are extremely ‘plastic’ and can respond to a variety of cues encountered during virion entry enabling the use of either the ‘early’ or ‘late’ pathway, depending on the host cell type and microenvironmental conditions. NTD = N-terminal domain of S1, CTD = C-terminal domain of S1.