literature

SARS_CoV_2 mutation literature information.

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

Discussion: Some substitutions specific to the Omicron spike protein near the prefusion-stabilizing 2P mutations (K986P and V987P) used in mRNA vaccines could help stabilize conformations that expose shared epitopes between the D614G vaccine antigen and Omicron.

Evolution of the SARS-CoV-2 spike protein in the human host.

PMID: 35246509 2022 Nature communications

Method: The variant spikes were stabilised in the pre-fusion conformation (K986P and V987P) with the furin-cleavage site ([PH]RRAR) either intact ('2P' constructs) or mutated to the uncleavable sequence PSRAS ('FUR2P' constructs).

Conformational Flexibility and Local Frustration in the Functional States of the SARS-CoV-2 Spike B.1.1.7 and B.1.351 Variants: Mutation-Induced Allosteric Modulation Mechanism of Functional Dynamics and Protein Stability.

PMID: 35163572 2022 International journal of molecular sciences

Introduction: The S-GSAS construct showed similar structural, antigenic, and stability behavior as the S-GSAS/PP construct, which included the K986P and V987P mutations.

Method: The glycosylated microenvironment for atomistic models of the simulation trajectories was mimicked by using the structurally resolved glycan conformations for 22 most occupied N-glycans in each as determined in the cryo-EM structures of the SARS-CoV-2 spike S trimer in the closed state (K986P/V987P,) (pdb id 6VXX) and open state (pdb id 6VYB), and the cryo-EM structure SARS-CoV-2 spike trimer (K986P/V987P) in the open state (pdb id 6VSB).

Breadth of SARS-CoV-2 Neutralization and Protection Induced by a Nanoparticle Vaccine.

PMID: 35118474 2022 bioRxiv

Method: In the second study, cynomolgus macaques (n=5) were were immunized twice with 50 mug of S-2P mRNA-LNP (encoding the transmembrane spike protein stabilized with K986P and V987P mutations) and boosted once with 100 mug of RBD-scNP, NTD-scNP and S2P-scNP adjuvanted with 5 mug of 3M-052 aqueous formulation admixed with 500 mug of alum in PBS.

Method: The S-2P mRNA was designed based on the SARS-CoV-2 spike (S) protein sequence (Wuhan-Hu-1) and encoded the full-length S with K986P and V987P amino acid substitutions.

Enhanced fitness of SARS-CoV-2 variant of concern Alpha but not Beta.

PMID: 34937050 2022 Nature

Method: SARS-CoV-2 S protein expression plasmids were constructed to encode the ectodomain of S protein S(D614G) or SAlpha (residues 1-1208, with a mutated furin cleavage site and K986P/V987P substitutions) followed by a T4 fold on the trimerization domain and a polyhistidine purification tag.

Neutralizing activity of Sputnik V vaccine sera against SARS-CoV-2 variants.

PMID: 34312390 2021 Nature communications

Table: V987P

Discussion: Three of the six COVID-19 vaccines currently in use worldwide, namely Moderna mRNA-1273, BioNTech BNT162b2, and Janssen Ad26.COV2.S, each express S harboring K986P and V987P substitutions (2P) within a loop abutting the central helix of the S2' membrane fusion machinery.

An Intranasal OMV-Based Vaccine Induces High Mucosal and Systemic Protecting Immunity Against a SARS-CoV-2 Infection.

PMID: 34987509 2021 Frontiers in immunology

Figure: Not shown: six stabilizing prolines in S2 at positions F817P, A892P, A899P, A942P, K986P, and V987P.

N-glycosylation profiles of the SARS-CoV-2 spike D614G mutant and its ancestral protein characterized by advanced mass spectrometry.

PMID: 34876606 2021 Scientific reports

Method: The sequences of the two proteins include mutated furin cleavage site and K986P, V987P substitutions.

Molecular switches regulating the potency and immune evasiveness of SARS-CoV-2 spike protein.

PMID: 34611654 2021 Research square

Method: SARS-CoV-2 spike ectodomains (residues 1-1211) were cloned into the vector containing mutations of interest, in addition to two proline mutations in S2 (K986P, V987P), a C-terminal foldon trimerization tag, and a C-terminal His6-tag.

Systemic effects of missense mutations on SARS-CoV-2 spike glycoprotein stability and receptor-binding affinity.

PMID: 33006605 2021 Briefings in bioinformatics

Discussion: SARS-Cov-2 mutations K986P and V987P have the minimum DeltaDeltaG values at -0.839 and -1.999 kcal/mol, respectively.

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