Introduction: For example, we observed the emergence of the P681R mutation in the U.S.
Introduction: The Omicron variants thus far display the P681H mutation observed in earlier Alpha variants, unlike the P681R mutation observed in Delta, which has been documented experimentally to contribute to increased infectivity.
The dynamics of circulating SARS-CoV-2 lineages in Bogor and surrounding areas reflect variant shifting during the first and second waves of COVID-19 in Indonesia.
Discussion: However, functional assays showed that the S_P681R substitution on its own is not enough to promote enhanced infectivity and transmissibility associated with variants bearing this mutation .
Discussion: On the other hand, substitutions in the region encoding the spike protein in Indonesian lineages mainly consisted of
Discussion: Similarly, increased infection due to enhanced cleavage of the S protein has also been associated with the presence of S_P681R mutation, leading to improved viral replication efficiency of Delta variant compared to the Alpha variant .
Discussion: The presence of the S_N439K and S_ P681R substitutions in the Indonesian lineages are important to note, as these mutations have been shown to confer certain advantages for the variants.
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
Molecular definition of severe acute respiratory syndrome coronavirus 2 receptor-binding domain mutations: Receptor affinity versus neutralization of receptor interaction.
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 (wild-type) or lineage defining mutations for Beta (L18F, D80A, D215G, 241-243del, K417N, E484K, N501Y, D614G and Result: Amino acid substitutions close to the furin cleavage site, including H655Y and P681R/H, have been shown to increase S1/S2 cleavage efficiency, and have also been observed in other VOCs and VOIs, such as Alpha, Delta, Gamma, Mu, and Kappa (S1/S2 region in.
SARS-CoV-2 BA.1 variant is neutralized by vaccine booster-elicited serum, but evades most convalescent serum and therapeutic antibodies.
PMID: 35380448
2022
Science translational medicine
Result: We compared the neutralization titers of these serum samples against pseudoviruses bearing spike proteins from the following variants: D614G, Omicron (A67V, del69-70, T95I, del142-144, Y145D, del211, L212I, ins214EPE, G339D, S371L, S373P, S375F, K417N, N440K, G446S, S477N, T478K, E484A, Q493R, G496S, Q498R,
Multiple SARS-CoV-2 Variants Exhibit Variable Target Cell Infectivity and Ability to Evade Antibody Neutralization.
Discussion: In fact, B.1.617.2 contains the P681R mutation, which results in enhanced cleavage of the S protein in cells, which may account for the enhanced infectivity of B.1.617.2 in some susceptible cells.
Discussion: The P681H, P681R, and Q677H mutation sites in the variants are located near the furin cleavage site, which may affect the cleavage of S protein.
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.
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.
Result: Analytic LoD was determined by 2-fold dilution series (8 steps, 8 repeats) as 19.0 IU/mL (CI95%: 12.9-132.2 IU/mL) for target 1: A67V + del-HV69-70; 105.0 IU/mL (CI95%: 80.7-129.3 IU/mL) for target 2: P681R; 193.9 IU/mL (CI95%: 144.7-334.7 IU/mL) for target 3: E484A; and 35.5 IU/mL (CI95%: 23.3-158.0 IU/mL) for target 4: N679K +P681H
Delta Variant with P681R Critical Mutation Revealed by Ultra-Large Atomic-Scale Ab Initio Simulation: Implications for the Fundamentals of Biomolecular Interactions.
Result: Most of these studies focus on the clinical or experimental observations to demonstrate the danger of mutations, especially the P681R near the furin cleavage site in the SD2-FP domain of the S-protein, but, to the best of our knowledge, no theoretical explanation or computational studies have been reported so far.
Result: Table S2 lists the structure information from VASP optimization for the four SD2-FP models in the Delta variant: (a) wild type (WT), (b) mutated P681R (R681), (c) mutated D614G (G614), and (d) double mutation (DM) labeled as G614-R681.
Discussion: Importantly, the P681R mutation reduces the local rigidity, as evidenced by the NN AABP values (Table 1).
Discussion: The data in Table 1 reveal that D614G and P681R
Evolution of the SARS-CoV-2 spike protein in the human host.
Result: Our data suggest that this substitution P681R in Kappa and Delta spikes, as well as P681H in Omicron spike, will also increase stability of the receptor-bound form of these spikes, accounting at least in part for their increased transmissibility.
Result: The recent variants of concern B.1.617 (Kappa) and B.1.617.2 (Delta) contain the substitution P681R, which also results in full cleavage.
SARS_CoV_2 mutation literature information.
PMID: 
2022
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