Conformational Flexibility and Local Frustration in the Functional States of the SARS-CoV-2 Spike B.1.1.7 and B.1.351 Variants: Mutation-Induced Allosteric Modulation Mechanism of Functional Dynamics and Protein Stability.
PMID: 35163572
2022
International journal of molecular sciences
Result: Although modifications of A570D are generally destabilizing, the range of free-energy changes associated with this position suggested a moderate level of residual energetic frustration and suboptimal interactions (Figure 8).
Result: Another interesting observation is the emergence of A570D and D614G mutational sites as the key inter-protomer hinges that can orchestrate functional movements in the S-B.1.1.7 conformations (Figure 6C,D).
Result: At the same time, the key hinge position A570D showed a similar relative density of neutral and minimal frustration.
Result: Collective Modes of the SARS-CoV-2 S Protein Variants Reveal Role of A570D and D614G in the Hinge Regions Controlling Transitions between Open and Closed States.
Mass Screening of SARS-CoV-2 Variants using Sanger Sequencing Strategy in Hiroshima, Japan.
Method: The initial checkpoint was set at nucleotide position nt23063 and if we found mutation from adenine (A) to thymine (T) at nt23063, further identification was done as follows: double mutation of A23063T (referred to N501Y) and C23271A (referred to A570D) for B.1.1.7 (Alpha), G23013A (referred to E484K) and A23063T for B.1.351 (Beta) and triple mutation of G23012A, A23063T and C23525T (referred to H655Y) for P.1 (Gamma).
Genomic Diversity of SARS-CoV-2 in Algeria and North African Countries: What We Know So Far and What We Expect?
Discussion: Comparative genomic analysis of SARS-CoV-2 genomes revealed multiple crucial mutations to the Spike gene including K417N, K417T, E484K, N501Y, A570D, D614G, P681H, T716I, S982A and D1118H, which may aggravate the severity of SARS-CoV-2 more than the wild type variant, and potentially raise the concern of vaccine efficacy against novel strains.
Allosteric Determinants of the SARS-CoV-2 Spike Protein Binding with Nanobodies: Examining Mechanisms of Mutational Escape and Sensitivity of the Omicron Variant.
PMID: 35216287
2022
International journal of molecular sciences
Introduction: Using data analysis and protein structure network modeling of MD simulations, residues that exhibit long-distance coupling with the RBD opening, including sites harboring functional mutations D614G and A570D, which points to the important role of the D614G variant in modulating allosteric communications in the S protein.
Deep learning based on biologically interpretable genome representation predicts two types of human adaptation of SARS-CoV-2 variants.
Abstract: The identified adaptive determinants included D1118H and A570D mutations and local DNTs.
Evolutionary history of the SARS-CoV-2 Gamma variant of concern (P.1): a perfect storm.
PMID: 35266951
2022
Genetics and molecular biology
Introduction: Nine key mutations involving the S glycoprotein have been identified: 69/70del, 144del, N501Y, A570D, D614G, P681H, T716I, S982A, and D1118H.
SARS-CoV-2 Beta and Delta variants trigger Fc effector function with increased cross-reactivity.
Method: The SARS-CoV-2 Wuhan-1 spike, cloned into pCDNA3.1 was mutated using the QuikChange Lightning Site-Directed Mutagenesis kit (Agilent Technologies) and NEBuilder HiFi DNA Assembly Master Mix (NEB) to include D614G (original) or lineage defining mutations for Alpha (DEL69-70, DEL144, N501Y, A570D, D614G, P681H, T716I, S982A, D1118H), Beta (L18F, D80A, D215G, 242-244del, K417N, E484K, N501Y, D614G and A701V<
Evolution of the SARS-CoV-2 spike protein in the human host.
Method: The following variant spikes were made (SA, Alpha and mink) (all mutations listed with reference to the NCBI sequence YP_009724390.1): 2P Alpha (Delta69-70, Delta144, N501Y, A570D, D614G, P681H, T716A, S982A, D1118H, and K986P, V987P), FUR2P Alpha (Delta69-70, Delta144, N501Y, A570D, D614G, T716A, S982A, D1118H, and R682S, R685S, K
SARS-CoV-2 monoclonal antibodies with therapeutic potential: Broad neutralizing activity and No evidence of antibody-dependent enhancement.
Abstract: Residues involved in the most ubiquitous D614G mutation and the A570D mutation of the highly contagious UK SARS-CoV-2 variant are predicted ab initio from our model.
Introduction: In fact, the most ubiquitous spike protein mutation to date, the D614G, and the A570D mutation in the recently emerged highly contagious UK SARS-CoV-2 strain both appeared among our predicted set of residues, the latter having been discovered after the completion of our calculations.
Result: On the contrary, an A570D mutation is observed in the same residue in the newly emerged and highly infectious B.1.1.7 strain in the United Kingdom.
Discussion: However, a different mutation at residue 570 (A570D) has indeed appeared in the recently emerged m