Recent progress on the mutations of SARS-CoV-2 spike protein and suggestions for prevention and controlling of the pandemic.
PMID: 34146731
2021
Infection, genetics and evolution
Abstract: Among these mutations, the most representative ones are substitution mutations such as D614G, N501Y, Y453F, N439K/R, P681H, K417N/T, and E484K, and deletion mutations of DeltaH69/V70 and Delta242-244, which confer the virus with enhanced infectivity, transmissibility, and resistance to neutralization.
Introduction: Among the mutations in the B.1.1.7, nine mutations, including H69-V70 deletion (Delta69/Delta70), Y144 deletion (Delta144), N501Y, A570D, D614G, P681H, T716I, S982A, and D11
Epitope Classification and RBD Binding Properties of Neutralizing Antibodies Against SARS-CoV-2 Variants of Concern.
Discussion: If increased ACE2 affinity is required for increasing viral infectivity, other mutations in the SARS-CoV-2 S, such as D614G, P681H, or several other changes, alone or together, must be responsible for enhanced ACE2 binding affinity.
Tracking SARS-CoV-2 Spike Protein Mutations in the United States (2020/01 - 2021/03) Using a Statistical Learning Strategy.
Result: It is natural to name the haplotype T478K-D614G-P681H-T732A as a B.1.1.222.
Result: The P681H mutation occurs in the S1/S2 cleavage segment of the Spike protein, which is typically not resolved in cryo-electron microscopy or x-ray diffraction experiments.
Preliminary Structural Data Revealed That the SARS-CoV-2 B.1.617 Variant's RBD Binds to ACE2 Receptor Stronger Than the Wild Type to Enhance the Infectivity.
Introduction: These mutations in this strain may enhance virus transmissibility and infectivity, including the deletion of residues 69-70 and 144 and the substitution of A570D, D614G, T716I, S982A, D1118H, P681H, K417N, K417T, E484 K and N501Y.
Recurrent emergence of SARS-CoV-2 spike deletion H69/V70 and its role in the Alpha variant B.1.1.7.
Method: The mutations (Delta69/70, Delta144, N501Y, A570D,
Result: In addition to RBD N501Y and NTD DeltaH69/V70, B.1.1.7 is defined by further S mutations across S2 (T716I, S982A, and D1118H) and S1 (DeltaY144, A570D, and P681H) (Figure 6A).
Discussion: In addition, a recent report on the S1/S2 cleavage site mutation P681H demonstrated that enhanced cleavage of spike P681H was not associated with increased PV infectivity or cell fusion relative to the WT.
Analysis of SARS-CoV-2 variant mutations reveals neutralization escape mechanisms and the ability to use ACE2 receptors from additional species.
Introduction: A few mutations in the SD1-2 region near the Furin cleavage site are also identified, such as P681H in B.1.1.7 and A701V in B.1.351.
Method: The variant B.1.1.7 (GISAID: EPI_ISL_601443) was constructed with total of 9 mutations including 69-70del, 144del, N501Y, A570D, D614G, P681H, T716I, S982A and D1118H.
Emergence in southern France of a new SARS-CoV-2 variant harbouring both N501Y and E484K substitutions in the spike protein.
Discussion: The large number of genomic mutations associated with B.1.1.7, including SNPs (A570D, D614G, P681H, T716I, S982A, and D1118H) highlight the need to rapidly distinguish these subtle mutations in emerging VOCs.
Ultrapotent miniproteins targeting the SARS-CoV-2 receptor-binding domain protect against infection and disease.
Result: Accordingly, we evaluated the activity of LCB1v1.3 against a B.1.1.7 isolate containing deletions at 69-70 and 144-145 and substitutions at N501Y, A570D, D614G, and P681H, and against a recombinant WA1/2020 strain containing key substitutions present in the B.1.351 and B.1.1.28 variant strains at residues E484K, N501Y, and D614G.
Occurrence of a novel cleavage site for cathepsin G adjacent to the polybasic sequence within the proteolytically sensitive activation loop of the SARS-CoV-2 Omicron variant: The amino acid substitution N679K and P681H of the spike protein.
Result: As the P681H mutation is also found in the B.1.1.7 variant, its frequency has increased in some locations since late December 2020, following the first introduction of B.1.1.7 into Israel.
Result: Characterization of the B.1.1.50 + P681H Variant.
Result: Effective Neutralization of the B.1.1.50 + P681H Variant.
Result: Identification of the P681H Mutation in Sewage.
Result: The B.1.1.50 + P681H variant is characterized by the non-synonymous S protein mutation P681H (C23604A) and four additional synonymous mutations: Nsp3:C7765T, Nsp12b:C13821T, Nsp16: