This workshop will focus on the roles of glycans in Coronavirus (CoV) infection, with emphasis on the Spike-glycoprotein of SARS-CoV-2, its host receptor(s) and it will introduce new research tools that can facilitate these studies and accelerate the development of therapeutics, vaccines and diagnostics.
Coronavirus (α−, β−, γ−, and δ-CoVs) are single stranded RNA viruses that can infect the lung, gastrointestinal, and central nervous system of mammals (α-, β-) and birds (γ-,δ-). While both α and β-CoV strains can cause mild infections in humans, three β-CoV strains (SARS-CoV in 2003; MERS-CoV in 2012; SARS-CoV-2 in 2019) have crossed species barrier to cause severe acute respiratory syndrome in humans. The infection process is facilitated by viral spike-glycoproteins (transmembrane, homotrimers). Each Spike glycoprotein is composed of two subunits (S1 subunit binds host receptor; S2 subunit promotes fusion of viral and cellular membranes), which undergo conformational change to bind to host cell receptor(s) and are subsequently proteolytically processed causing conformational changes that promote virus-cell fusion. Spike-glycoprotein trimers are extensively decorated with N-linked glycans. Likewise, the cellular protein(s) to which CoVs attach are also glycosylated. Glycosylation is known to play important roles in viral attachment, accessibility to host proteases, and modulating the host immune response. Given that spike glycoproteins mediate entry into host cells, they are targets for neutralizing antibodies (whose effector functions may also be modulated by glycosylation), therapeutics, and vaccines. It is thus important to understand the role(s) glycosylation plays in the viral infection process. The Common Fund Glycoscience Program is making tools that can facilitate these studies and speed progress.