A Comprehensive Molecular Epidemiological Analysis of SARS-CoV-2 Infection in Cyprus from April 2020 to January 2021: Evidence of a Highly Polyphyletic and Evolving Epidemic.
Result: In the B.1.258 lineage, three mutations, F374I, K417N and K528E, were detected in the RBD and were found in different sequences.
Result: Interestingly, the K417N mutation was reported to be one of the lineage-defining mutations of South African lineage B.1.351.
Discussion: In one sequence in the B.1.258 lineage in this study, the K417N mutation was detected (Figure 2B).
Discussion: Interestingly, it has also been found that K417N weakens binding between the RBD and human ACE2, while other mutations, such as E484K, enhance binding.
Discussion: The independent evolution of certain mutations and deletions (DeltaH69/V70, PMID: 34208912
2021
Diagnostics (Basel, Switzerland)
Result: The E484K or K417N/T mutations co
Discussion: Since the neutralization activities of the bin A antibodies (Ab1 and Ab4) were not affected by the three mutations contained in the UK, SA, and BR P.1 variant RBDs, further investigation of the mechanism by which the E484K or K417N/T alters the binding and neutralizing activities of these antibodies may help in the identification of a better therapeutic epitope target.
Discussion: This discriminative binding behavior to the four RBDs suggests that the E484K or K417N/T mutations likely induced conformational changes near the epitopes, where these antibodies bind in the SA and BR P.1 variant RBDs.
The emerging SARS-CoV-2 variants of concern.
PMID: 34211709
2021
Therapeutic advances in infectious disease
Introduction: The 501Y.V2 variant has been detected in many countries outside of South Africa and is characterized by mutations in the S protein, including residues in the RBD:K417N, E484K, and N501Y.
Discussion: However, the study further showed that variants that carry K417N/T, E484K, and N501Y mutations, such as the UK (B1.1.7/501Y.V1), South African (501Y.V2), and Brazil (B1.1.28/501.V3) variants, can reduce the neutralization potency of vaccine plasma.
Insilico study on the effect of SARS-CoV-2 RBD hotspot mutants' interaction with ACE2 to understand the binding affinity and stability.
Introduction: 20H/501Y.V2) was identified in Nelson Mandela Bay, South Africa, with multiple S protein mutations, including K417N, E484K and N501Y.
Introduction: A variant named Delta plus or AY.1 has been identified in India with the point mutation K417N.
Result: Consistently, the variant K417N has the highest binding free energy (-51.25 kcal/mol) with a difference of -8.41 kcal/mol from the WT (-59.66 kcal/mol), resulting in the lowest binding affinity between the ACE2 and RBD complex.
Result: The mutant K417N has the next minimum DeltaDeltaG value.
Table: K417N
Antibody Cocktail Exhibits Broad Neutralization Activity Against SARS-CoV-2 and SARS-CoV-2 Variants.
Introduction: The recent emerging variants of concern observed in the United Kingdom (B.1.1.7 with mutations N501Y, A570D and del69/70), South Africa (B.1.351 with mutations K417N, E484K and N501Y), Brazil (P.1 and P.2 with mutations K417T, E484K and N501Y) (Long et al.) and India (B.1.617 with mutations L452R and E484Q) (Cherian et al.) initially respond more tightly to ACE2 and appear to be more infectious to human (Laffeber et al.; Tian et al.).
Figure: D Neutralization activities of F61 and H121 towards mutations K417N, E484K, and N501Y
A bivalent recombinant vaccine targeting the S1 protein induces neutralizing antibodies against both SARS-CoV-2 variants and wild-type of the virus.
Result: Based on D614G, other mutations existing in RBD are K417N/K417T, E484K, and N501Y which might affect the recognition and binding of SARS-CoV-2 to ACE2.
Genomic monitoring unveil the early detection of the SARS-CoV-2 B.1.351 (beta) variant (20H/501Y.V2) in Brazil.
Result: The B.1.351 VOC was characterized by K417N, E484K, N501Y in the spike region and 19 mutations and 2 deletions as follows: ORF1ab: T265I, R724K, S1612L, K1655N, K3353R, SGF 3675_F3677del, P4715L, E5585D; spike: D80A, D215G, L242_L244del, A262D, D614G, C1247F; ORF3a: Q57H, PMID: 34244522
2021
Nature communications
Abstract: However, virus escape analysis identifies a single natural mutation in RBD, namely K417N found in B.1.351 variant from South Africa, abolished the neutralizing activity of these public antibodies.
Method: Specifically, protein A (Sino Biological) was firstly covalently immobilized onto a CM5 sensor chip, followed by capture of the individual antibodies and then injection of purified soluble SARS-CoV-2 WT and K417R/A/E/N/T mutant RBDs at five different concentrations.
Result: K417A/E/N/T mutants resulted in complete resistance to P5A-3C8, P2
Result: In contrast, K417A/E/N/T mutants substantially reduced binding by P22A-1D1 and P5A-1D2, while impact on P5A-3C8 and P2C-1F11 was relatively moderate.
SARS-CoV-2 B.1.617 Indian variants: Are electrostatic potential changes responsible for a higher transmission rate?