Comparative mutational analysis of SARS-CoV-2 isolates from Pakistan and structural-functional implications using computational modelling and simulation approaches.
PMID: 34968862
2022
Computers in biology and medicine
Result: Interestingly, among all recurrent mutations in structural protein, the spike protein has one D614G (82%), nucleocapsid had three S194L (20%), R203K (14%), G204R (14%) R209I (25%) mutation hotspot.
Result: Surprisingly, in the spike protein, the D614G substitution was associated with two consecutive series of two substitutions R203K, and G204R of the nucleocapsid phosphoprotein in five isolates (MW031799.1, MW031800.1, MW031801.1, MW0831802.1, and MW031803.1).
Table: G204R
Plasticity in structure and assembly of SARS-CoV-2 nucleocapsid protein.
Result: The earlier R203K/G204R was shown experimentally to enhance the ability of N-protein to form condensates, and R203M - prevalent in the Delta variant - was recently reported to enhance viral replication.
Discussion: Earlier examinations of emerging mutations in N proteins, going back to June 2020, were necessarily more limited in scope, and while sufficient to examine hot spots and identify key replacements such as R203K/G204R, it was not yet possible to draw conclusions from a survey of the entire mutational landscape.
Clinical and genomic data of sars-cov-2 detected in maternal-fetal interface during the first wave of infection in Brazil.
Result: Sequences from this study also share four nonsynonymous mutations, P314L (Nsp12), D614G (Spike), R203K and G204R (Nucleocapsid), with these placenta sequences, in addition to two synonymous mutations (214C>T, 3037 C>T).
Discussion: A critical polymorphic region of this protein is the serine-arginine region located in amino acids 183-206, exactly where the R203K and G204R aa changes locate.
Discussion: Mutations R203K/G204R in the Nucleocapsid gene, were found in both sequences.
SARS-CoV-2 genomes from Saudi Arabia implicate nucleocapsid mutations in host response and increased viral load.
Figure: Higher viral loads in samples with R203K/G204R SNPs.
Figure: On both plots, lines show the fraction of samples having the R203K/G204R SNPs (red line), having both the R203K/G204R SNPs and the Spike
Figure: a A schematic diagram showing the SARS-CoV-2 N protein different domains (Upper: control, Lower: mutant) and highlighting the mutation site (R203K and G204R) and the linker region (LKR) containing a serine-arginine rich motif (SR-motif).
Figure: b Overview of the three SNPs underlying the N protein R203K/G204R changes.
Whole-Genome Sequencing of SARS-CoV-2 Strains from Asymptomatic Individuals in India.
Discussion: Among these six SNVs, four nucleotides (c28854, g28881, g28882, g28883) were non-synonymous and code residues S194L, R203K, R203S and G204R, respectively, in Nucleocapsid, and two nucleotides (t19839, a20268) in endoRNase of orf1ab encoded synonymous changes
Discussion: The non-synonymous mutations R203K, R203S and G204R in the nucleocapsid protein all occur in the flexible linker region between the N-terminal RNA-binding domain and the C-terminal dimerization domain, and this linker segment is not resolved in any reported cryo-EM or x-ray structures.
Discriminatory Weight of SNPs in Spike SARS-CoV-2 Variants: A Technically Rapid, Unambiguous, and Bioinformatically Validated Laboratory Approach.
Discussion: In particular, single high-frequency SNPs in SARS-CoV-2 were found on the spike glycoprotein (D614G, 23364 A > G), as well as in the protein encoding for the nucleocapsid (R203K, R202R, and G204R).
Genetic variations from successive whole genome sequencing during COVID-19 treatment in five individuals.
PMID: 35035981
2022
New microbes and new infections
Table: G204R
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.
SARS_CoV_2 mutation literature information.
PMID: 
2022
Computers in biology and medicine
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