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.
Abstract: In the spike protein gene, S_D614G and S_P681R changes were dominant in both B.1.466.2 and Delta variants, while N439K was only observed in B.1.466.2 (n = 44) and B.1.470 (n = 1).
Figure: One virus (hCoV-19/Indonesia/JK-LIPI135/2021) not shown in this figure was found to carry multiple amino acid changes, including S_D614G, S_P681R, S_T478K, S_L452R, NSP6_T77A, NSP3_P1228L, NSP12_P323L, NSP12_G671S, and NSP14_
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.
4Method: The multiplex assay amplifies three regions of the SARS-CoV-2 S-gene: 102bp within the N-terminal domain (NTD) (probe 1: ""SDEL2""), 353/80bp within the receptor-binding-domain (RBD) (probe 3, ""E484A""), and 95bp at the furin-cleavage-site (probe 2: ""
Method: Five interactions were analyzed further due to high binding energy (RBD-484-fwd: RBD-484-fwd (2x), P681-fwd: P681fwd, RBD-484-fwd: P681R-probe, RBD-484-fwd: P681H-probe) (Supplementary Figure S1).
Method: For the P681R target, a clinical Delta-variant sample (confirmed by NGS) was normalized to WHO standard using the same method.
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.
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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