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: Mutation R203K in nucleocapsid protein was observed in 151 countries.
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, MW031
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 (N73N and L216L, respectively).
Discussion: The mutations R203S and G204R are non-conservative and even the R203K mutation is often observed to function as a non-conservative substitution in many cases, due to the different size of the R versus K residues and the notably different chemical feature
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
Introduction: In the first patient, we found substitution at position N:S255A and S:N501Y on the first swab and revert back to its original sequence on the second swab and additional substitution at N:R203K and N:S235F.
Introduction: Last patient, we found substitutions at N:D3Q and ORF1b:P314L on the first swab and reversion of both substitutions with addition substitution at N:R203K on the second swab.
Introduction: Second patient, we found substitution at position N:R20
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: The remaining Indian sequences continued to harbour the R203K and G204R mutations, which were present since May 2020.
Developing an Amplification Refractory Mutation System-Quantitative Reverse Transcription-PCR Assay for Rapid and Sensitive Screening of SARS-CoV-2 Variants of Concern.
Introduction: Since there are multiple mutations in variants, the current ARMS-PCR methods for screening SARS-CoV-2 variants depend on the combination of multiple hot spot mutations, such as D614G and R203K.
Nucleocapsid mutations in SARS-CoV-2 augment replication and pathogenesis.
Abstract: Importantly, the R203K+G204R mutation increases nucleocapsid phosphorylation and confers resistance to inhibition of the GSK-3 kinase, providing a molecular basis for increased virus replication.
Abstract: Recreating a mutation found in the alpha and omicron variants in an early pandemic (WA-1) background, we find that the R203K+G204R mutation is sufficient to enhance replication, fitness, and pathogenesis of SARS-CoV-2.
Abstract: Recreating the prominent nucleocapsid R203K+G204R mutation in an early pandemic background, we show that this mutation is alone sufficient to enhance SARS-CoV-2 replication and pathogenesis.