Neutralisation Hierarchy of SARS-CoV-2 Variants of Concern Using Standardised, Quantitative Neutralisation Assays Reveals a Correlation With Disease Severity; Towards Deciphering Protective Antibody Thresholds.
Abstract: None of the mutations increased but several decreased S protein cleavage at the S1/S2 site, including S686G and P681H, the latter of which is found in variants of concern B.1.1.7 (Alpha variant) and B.1.1.529 (Omicron variant).
Discussion: A total of five mutations (P681H, P681L, A684S, S686G, V687L) were found to be associated with reduced S protein cleavage, with mutation S686G showing the lowest level of S protein cleavage.
Discussion: In contrast, Lubinski and colleagues and the present study demonstrate that P681H, which is found in the
Circulation of SARS-CoV-2 Variants among Children from November 2020 to January 2022 in Trieste (Italy).
Result: Finally, 1/32 sequence was the Omicron strain, with the following mutations in the RBD domain: T22882G (N440K), G22898A (G446S), G22992A (S477N), C22995A (T478K), A23013C (E484A), A23040G (Q493R), G23048A (G496S), A23055G (Q498R), A23063T (N501Y), T23075C ( PMID: 35336868
2022
Viruses
Introduction: Omicron has posed a serious public health concern due to the mutations/deletions associated with increased binding affinity to ACE2 (S:Q498R and S:N501Y), increased transmissibility (S:H655Y, S:N679K, and S:P681H), increased viral load (N:R203K and N:G204R), innate immune evasion (ORF1a:L3674-, ORF1a:S3675-, and ORF1a:G3676), and S-gene target failure (S:H69-).
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: In a first set of investigations, a prediction approach of cleavage sites for the SARS-CoV-1 660YHTVSLLRSTSQKS673, SARS-CoV-2 (Wuhan) 678TNSPRRARSVASQS691, SARS-CoV-2 P681H (Alpha) 678TNSHRRARSVASQS691, and SARS-CoV-2 P681R (Delta) 678TNSRRRARSVASQS691, SARS-CoV-2 N679K (C.1.2) 674YQTQTKSPRRARSVASQS691, and SARS-CoV-2 N679K P681R (Omicron) 674YQTQTKSHRRARSVASQS691.
Result: In order to verify these results experimentally, SARS-CoV-1, SARS-CoV-2 (Wuhan), SARS-CoV-2 P681H (Alpha), and SARS-CoV-2 P681R (Delta), SARS-CoV-2 N679K (C.1.2), and SARS-CoV-2 N679K P681R (Omicron) peptides were synthesized and incubated with the indicat
Clinical Evaluation of a Fully-Automated High-Throughput Multiplex Screening-Assay to Detect and Differentiate the SARS-CoV-2 B.1.1.529 (Omicron) and B.1.617.2 (Delta) Lineage Variants.
4Method: By using this approach, we generated two Omicron ""specific"" targets (A67V
7Figure: Omicron variant (Non-BA.2) sequences are expected to contain A67V + del-HV69-70 (probe 1, ""SDEL2""), E484A (probe 3, ""E484A"") and N679K + P681H (probe 4, ""P681H"")."
Abstract: Analytic sensitivity was determined as 19.0 IU/mL (CI95%: 12.9-132.2 IU/mL) for the A67V + del-HV69-70 target, 193.9 IU/mL (CI95%: 144.7-334.7 IU/mL) for the E484A target, 35.5 IU/mL (CI95%: 23.3-158.0 IU/mL) for the N679K + P681H target and 105.0 IU/mL (CI95%: 80.7-129.3 IU/mL) for the P681R target.
E-Volve: understanding the impact of mutations in SARS-CoV-2 variants spike protein on antibodies and ACE2 affinity through patterns of chemical interactions at protein interfaces.
Introduction: The Alpha variant fastly spread across dozens of countries and carried 17 mutations, including eight in the spike protein (HV 69-70 deletion, Y144 deletion, N501Y, A570D, P681H, T761I, S982A, and D1118H), which are the basis of three COVID-19 vaccines licensed.
Molecular Dynamics and MM-PBSA Analysis of the SARS-CoV-2 Gamma Variant in Complex with the hACE-2 Receptor.
Introduction: The alpha variant has three mutations of interest in the spike protein: (i) the N501Y mutation that corresponds to the receptor-binding motif (RBM); (ii) a 69/70 deletion in the receptor binding domain (RBD) that triggers a notable change in the conformation of the RBM; and (iii) the P681H mutation found near the furin S1/S2 cleavage site.
Antigenicity comparison of SARS-CoV-2 Omicron sublineages with other variants contained multiple mutations in RBD.
Result: Analysis of the wild-type C/H-CrUPs and the new formed, mutation-induced, C/H-CrUPs in Spike protein unveiled that the mutation-driven, novel, peptides are created exclusively around the critical R685 S cleavage site by the two pathogenic mutations P681H and P681R (Table 5 ).
Table: P681H
Figure: Green lines indicate the new created mutant C/H-CrUPs that derive from the P681H and P681R mutations in Alpha and Delta variants, respectively.
Figure: Red lines denote C/H-CrUPs produced by the P681H and P681R mutations.
SARS_CoV_2 mutation literature information.
PMID: 
2022
Frontiers in immunology
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