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: Of 379 severe acute respiratory syndrome coronavirus 2 samples collected in New York, USA, we detected 86 Omicron variant sequences containing Delta variant mutation P681R.
Abstract: Repeated library preparation with fewer cycles showed the P681R calls were artifactual.
Introduction: A total of 59 samples showed P681H on this repeated testing; only 2 still showed P681R, 1 at 0.52 frequency (down from 0.98) and 1 at 0.94, exactly as the previous sequence, suggesting a true P681R call, possibly co-infection with Delta, because the Ct for this sample was low (Ct = 17).
Introduction: Amplification artifact in SARS-CoV-2 Omicron sequences carrying P681R mutation, New York, USA.
Introduction: Clo
Table: P681R
SARS-CoV-2 multiplex RT-PCR to detect variants of concern (VOCs) in Malaysia, between January to May 2021.
PMID: 35026305
2022
Journal of virological methods
Introduction: The most recent VOC B.1.617.2 contains L452R and P681R mutations.
Discussion: However, new important variants such as B.1.617.1 (kappa), B.1.617.2 (delta) and B.1.617.3 have subsequently emerged, with mutations such as L452R and P681R that are not detected by these assays, necessitating additional panels.
Emergence of a novel SARS-CoV-2 Pango lineage B.1.1.526 in West Bengal, India.
PMID: 34896696
2022
Journal of infection and public health
Introduction: Along with the clade specific mutations, these variants have their own sets of characteristics mutations including several mutations in the S glycoprotein like Delta69-70, Delta144-145, N501Y, A570D, P681H, T716I, S982A, D1118H in the Alpha variant; D80A, D215G, Delta241-243,
Discussion: Though the role of D614G in increased infectivity and transmissibility is well known, the functional relevance of P681H/R (previously observed in Alpha variant and Delta variant) and V1230L (first detected in this study) is yet to be determined.
Efficacy of mRNA, adenoviral vector, and perfusion protein COVID-19 vaccines.
Introduction: Consequently, ten mutations in the spike protein of B.1.617.2 strain, including T19R, (G142D*), 156/157del, R158G, L452R, T478K, D614G, P681R, and D950N were identified.
Table: P681R
Two short low complexity regions (LCRs) are hallmark sequences of the Delta SARS-CoV-2 variant spike protein.
Abstract: The presence of the medically-important point mutations P681R and D950N in these LCRs, combined with the ubiquity of these regions in the highly contagious Delta variant opens the possibility that they may play a role in its rapid spread.
Discussion: In vitro experiments and SARS-CoV-2 infections in animal models have demonstrated that the P681R mutation enhances both the fusogenicity and pathogenicity of the virus.
Discussion: The mutation P681R detected in the Spike LCR-3 (SRRRARSVASQSIIA).
Genetic variations from successive whole genome sequencing during COVID-19 treatment in five individuals.
PMID: 35035981
2022
New microbes and new infections
Table: P681R
A novel antibody against the furin cleavage site of SARS-CoV-2 spike protein: Effects on proteolytic cleavage and ACE2 binding.
Abstract: Using a series of innovative ELISA-based assays, this furin site blocking antibody displayed high sensitivity and specificity for the S1/S2 furin cleavage site, including with a P681R mutation, and demonstrated effective blockage of both enzyme-mediated cleavage and spike-ACE2 interaction.
Discussion: Based on our results, peptide containing the P681R mutant SARS-CoV-2-specific furin motif indeed was more susceptible to cleavage by furin than the wild type site, and fbAB treatment was able to significantly reduce the cleavage percentage.
Discussion: In contrast, the mutation of P681H (Alpha
Discussion: fbAB demonstrated effective blockage of SARS-CoV-2 wide type and/or P681R S1/S2 furin site cleavage caused by purified furin enzyme, the serine protease trypsin, and human nasal swab specimens.
Developing an Amplification Refractory Mutation System-Quantitative Reverse Transcription-PCR Assay for Rapid and Sensitive Screening of SARS-CoV-2 Variants of Concern.
Result: It is worth noting that the hot spot amino acid substitutions currently of interest, such as N501Y, E484K, and P681R, were not unique or specific mutations able to differentiate the VOCs.
Emergence of two distinct variants of SARS-CoV-2 and an explosive second wave of COVID-19: the experience of a tertiary care hospital in Pune, India.
Result: All six Indian variants of the B.1.617.1 lineage exhibited five unique mutations: G142D, L452R, E484Q, P681R, and Q1071H.
Result: For the Delta variant, all six sequences belonged to B.1.617.2 lineage and had six unique mutations (T19R, G142D, L452R, T478K, P681R, and D950N).
Result: Notably, the position of the P681R mutation in the Kappa and Delta variants is immediately adjacent to the furin cleavage site (682-685).
Discussion: The rapid global spread of the UK variant with P681H and PMID: 34896524
2022
Gene