5Result: Notably, among these four new peptides (Table 5), the only one that embraces Furin's cleavage site is the ""SRRRAR S"" C/H-CrUP, which is solely generated by the P681R mutation carried by the Delta and Kappa
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 ).
Result: Most importantly, the SARS-CoV-2 Delta variant that carries the critical mutation P681R seems to be more infectious and pathogenic than the wild-type virus form, while the importance of this mutation has very recently begun to be recognized.
Molecular definition of severe acute respiratory syndrome coronavirus 2 receptor-binding domain mutations: Receptor affinity versus neutralization of receptor interaction.
Spike protein cleavage-activation mediated by the SARS-CoV-2 P681R mutation: a case-study from its first appearance in variant of interest (VOI) A.23.1 identified in Uganda.
Abstract: However, these changes in infectivity were not reproduced in the original Wuhan-Hu-1 spike bearing only the P681R substitution.
Abstract: Our findings suggest that while A.23.1 has increased furin-mediated cleavage linked to the P681R substitution, which may affect viral infection and transmissibility, this substitution alone is not sufficient and needs to occur on the background of other spike protein changes to enable its full functional consequences.
Abstract: The A.23 viral lineage, characterized by three spike mutations F157L, V367F and Q613H, was first identified in COVID-19 cases from a Ugandan prison in July 2020, and then was identified in the gen
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.
Figure: 200 mug/ml SARS-CoV-2 N679K P681R (Omicron) peptide was incubated with equal amounts of CatG and NE (4 mug/ml, upper panel) or 4 mug/ml of CatG, furin, and NE for 2h at 37 C.
Discussion: Furthermore, the increased turnover capacity of furin and the fact that furin (CatG) controlled the processing of SARS-CoV-2 N679K P681R (Omicron) peptide in contrast to NE, indicate to target furin and, most likely, CatG with selective protease inhibitors as a logical consequence to interfere with the priming of the S protein.
Discussion: It has been suggested that proline at the position 681 in SARS-CoV-2 allows an addition of O-linked glycans to nearby residues, leading to the creation of a mucin-like domain that shields antigen processing, which is circumvented by the introduction of an arginine residue in
Delta variant (B.1.617.2) of SARS-CoV-2: Mutations, impact, challenges and possible solutions.
PMID: 35507895
2022
Human vaccines & immunotherapeutics
Abstract: The enhanced transmissibility of Delta variant has been associated with critical mutations such as D614G, L452R, P681R, and T478K in the S-protein.
RBD-mRNA vaccine induces broadly neutralizing antibodies against Omicron and multiple other variants and protects mice from SARS-CoV-2 challenge.
Abstract: The RBD-mRNA-induced antibodies exerted moderate neutralization against authentic B.1.617.2 and B.1.1.529 variants, and pseudotyped B.1.351 and P.1 lineage variants containing K417N/T, E484K, and N501Y mutations, the B.1.617.2 lineage variant harboring L452R, T478K, and P681R mutations, and the B.1.1.529 lineage variant containing 38 mutations in the S protein.
SARS-CoV-2 mutations acquired during serial passage in human cell lines are consistent with several of those found in recent natural SARS-CoV-2 variants.
PMID: 35474907
2022
Computational and structural biotechnology journal
Introduction: For example, the D614G and P681R mutations in the spike protein were associated with increased viral replication in human lung epithelial cells and enhanced viral pathogenicity, respectively.
Functional Analysis of Spike from SARS-CoV-2 Variants Reveals the Role of Distinct Mutations in Neutralization Potential and Viral Infectivity.
Result: Our findings demonstrate that pseudoviruses carrying either Alpha-FCS-P681H mutation, Beta-A701V, or Delta-P681R efficiently transduce their target cells, and infectivity levels were similar to the levels exhibited by pseudoviruses that carried Wuhan wild-type P681 spike.
Result: The Delta spike carries unique RBD mutations including L452R, T478K, and P681R.
Result: These included either Alpha (P681H), Beta (A701V), or Delta (P681R) mutations.
Result: We conclude that FCS spike mutations PMID: 35434714
2022
MedComm
Result: P681H mutation in the Alpha and Omicron strains and P681R mutation in the Delta strain reduced the acidity of the amino acids, thereby improved furin recognition and the digesting efficiency, which means that more virus particles will enter the host cell.
Result: In the Delta strain, the L452R mutation seems to enhance antigenicity, whereas G142D has no effect on the epitope, but the P681R mutation seems to cause a slight decrease in the antigen score, which may have a certain effect on the epitope (Figure 2E).
Role of the Microbiome in the Pathogenesis of COVID-19.
PMID: 35433495
2022
Frontiers in cellular and infection microbiology
SARS_CoV_2 mutation literature information.
PMID: 
2022
Heliyon
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