Vulnerabilities in coronavirus glycan shields despite extensive glycosylation

Yasunori Watanabe; Zachary T. Berndsen; Jayna Raghwani; Gemma E. Seabright; Joel D. Allen; Jason S. McLellan; Ian A. Wilson; Thomas A. Bowden; Andrew B. Ward; Max Crispin

Coronaviruses (CoVs) are enveloped pathogens responsible for multiple respiratory disorders of varying severity in humans 1 These trimeric S proteins mediate host cell entry with the S1 and S2 subunits responsible for binding to the host cell receptor and facilitating membrane fusion, respectively [13] [14] [15] [16] [17] . MERS S binds to dipeptidyl-peptidase 4 (DPP4) 18 , whereas SARS S 19 and 2019-nCoV 20 utilize angiotensin-converting enzyme 2 (ACE2) as a host cellular receptor. CoV S proteins are the largest class I viral fusion proteins known 15 , and are extensively glycosylated, with SARS and MERS S glycoproteins both encoding 69 N-linked glycan sequons per trimeric spike with 2019-nCoV containing 66 sites. These extensive post-translational modifications often mask immunogenic protein epitopes from the host humoral immune system by occluding them with host-derived glycans 21, 22 . This phenomenon of immune evasion by molecular mimicry and glycan shielding has been observed and well characterised across other viral glycoproteins, such as HIV-1 envelope protein (Env) [23] [24] [25] , influenza hemagglutinin (HA) [26] [27] [28] and Lassa virus glycoprotein complex (LASV GPC) [29] [30] [31] .