The Impact of Natural and Glycosylation Mutations in the SARS-CoV-2 Spike Protein on Viral Infectivity and Antigenicity

The spike protein of SARS-Cov-2 has been undergoing mutations and is highly glycosylated. It is critically important to investigate the biological significance of these mutations. Here we investigated 80 natural mutants and 26 glycosylation mutants for the infectivity  and reactivity to a panel of neutralizing antibodies and sera from convalescent patients. D614G, along with several double mutations with D614G and another mutation in the same strains, were significantly more infectious, so was N149H, a glycosylation mutant. Most natural mutants within receptor binding domain were less infectious but some became more resistant to neutralizing antibodies. Moreover, the majority of glycosylation mutations were less infectious, revealing the importance of glycosylation for viral infectivity. Interestingly, N234Q was markedly resistant to neutralizing antibodies, whereas N165Q became more sensitive. These findings could be of value in informing our strategy for the development of vaccine and therapeutic antibodies. Funding: This work was supported by National Science and Technology Major Projects of Drug Discovery [grant number 2018ZX09101001] and National Science and Technology Major Projects of Infectious Disease [grant number 2017ZX10304402]. Conflict of Interest: All authors declare no competing interest.