The Impact of Mutations in SARS-CoV-2 Spike on Viral Infectivity and Antigenicity

Abstract

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 variants and 26 glycosylation site modifications for the infectivity and reactivity to a panel of neutralizing antibodies and sera from convalescent patients. D614G, along with several variants containing both D614G and another amino acid change, were significantly more infectious. Most variants with amino acid change at receptor binding domain were less infectious, but variants including A475V, L452R, V483A, and F490L became resistant to some neutralizing antibodies. Moreover, the majority of glycosylation deletions were less infectious, whereas deletion of both N331 and N343 glycosylation drastically reduced infectivity, 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 the development of vaccine and therapeutic antibodies.

Multi-site co-mutations and 5’UTR CpG immunity escape drive the evolution of SARS-CoV-2

“…Up to now, there were at least four dominant mutations (5'UTR_c-241-t, NSP3_c-3037-t, NSP12_c-14408-t, and S_a-23403-g) ( Fig. 1A), where S_ a-23403-g mutation resulted in the amino acid change (D614G) that enhances viral infectivity (6,16), albeit debate exists (10). In particular, each of them covered almost 100% of all virus sequences since the middle May 2020.…”

“…The mutation NSP2_c-1059-t resulted in an amino acid change (T85I) in the NSP2; the mutation NSP12_c-14408-t resulted in an amino acid change in the viral RNA-dependent RNA polymerase NSP12 (P323L) (Fig. 4B); the mutation S_a-23403-g resulted in an amino acid change in Spike protein (S)(D614G), which enhances viral infectivity (6,16); the mutation ORF3a_g-25563-t resulted in an amino acid change (Q57H) in Spike protein in ORF3a; the mutation NSP13_c-17747-t and NSP13_a-17858g resulted in an amino acid changes P504L and Y541C in the NTPase/helicase domain NSP13, respectively; the mutation ORF8_t-28144-c resulted in an amino acid change (L84S) in the ORF8; the mutations N_g-28881-a, N_g-28882-a, N_g-28883-c resulted amino acid changes R203K, R203S and G203R in the nucleocapsid N, respectively (Fig. 3P).…”

SARS-CoV-2 spike D614G variant exhibits highly efficient replication and transmission in hamsters

“…Attenuated variants with deletions in the spike protein S1/S2 junction and other regions have been detected in virus-infected cell cultures and in patient specimens (Lau et al, 2020b;Wong et al, 2020). One variant containing D614G in the spike protein has become the dominant population in many countries since March 2020 and is reported to infect cells more efficiently in vitro (Daniloski et al, 2020;Li et al, 2020;Zhang et al, 2020b). To understand if D614G variant virus may exhibit altered pathogenicity and transmissibility, we compared 5 SARS-CoV-2 isolates obtained from Hong Kong returnees from Wuhan, China, in February and travelers who had visited Europe and other countries after March 2020, using the hamster infection model.…”

Analytical validity of nanopore sequencing for rapid SARS-CoV-2 genome analysis

“…Integration with epidemiological data identifies transmission networks and can infer the origin of unknown cases [6][7][8][9][10][11][12] . Largescale, longitudinal surveillance by viral WGS may also provide insights into virus evolution, with important implications for vaccine development [13][14][15] .…”