Result: Four genetically linked mutations previously described as the globally dominant haplotype in April 2020 were found in the majority of our consensus sequences: C241T (100%; 5'UTR region), C3037T (98.6%; silent mutation), C14408T (100%; resulting in P4715L/P323L amino acid change in ORF1ab) and A23403G (100%; resulting in D614G amino acid change in S).
Discussion: As expected, the P323L change in the RNA-dependent RNA polymerase (RdRp), genetically linked to D614G, was also found
Genomic surveillance of Nevada patients revealed prevalence of unique SARS-CoV-2 variants bearing mutations in the RdRp gene.
Result: For the Wuhan isolate at 14,407 and 14,408 there is CC for proline (P), the variants have CT for leucine (P323L) and TT for phenylalanine (
Discussion: It is possible that these measures, compounded by potential inherent transmission variability of some viral isolates, influenced the change in the frequency of D614G, clades and P323L/F that we noted during this time period within Nevada.
Discussion: We performed structural modeling of the P323L/F variation and did not find any significant change to the nsp12 conformation with either P323L or P323F, therefore this variant is most likely a neutral mutation and does not confer either a fitness advantage or disadvantage to transmission or pathogenicity of SARS-CoV-2.
Mutation density changes in SARS-CoV-2 are related to the pandemic stage but to a lesser extent in the dominant strain with mutations in spike and RdRp.
Introduction: Soon after its spread to Europe and the US, a strain of SARS-CoV-2 with two non-synonymous mutations in the RNA-dependent RNA polymerase (RdRp) and spike (S) proteins, namely 14408 C>T (P323L) and 23403 A>G (D614G), became the dominant form particularly in Europe, and to some extent in the US, as well.
BioAider: An efficient tool for viral genome analysis and its application in tracing SARS-CoV-2 transmission.
PMID: 32904401
2020
Sustainable cities and society
Discussion: Among the triple linkage substitution hotspots of ORF1ab-277, ORF1ab-14144 and S-1841, ORF1ab-C2772T belongs to synonymous substitution, while ORF1ab-C14144T caused the aa change of NSP12-P323L in interface region which is a bridge section connecting NiRNA (nidovirus RdRp-associated nucleo-tidyltransferase) and Fingers of RdRp.
Coding-Complete Genome Sequences of Three SARS-CoV-2 Strains from Bangladesh.
Introduction: Compared with hCoV-19/Wuhan/WIV04/2019, for strain BCSIR-NILMRC-006, we found eight mutations, including NSP2_G339S, N_R203K, N_G204R, NSP3_Q172R, Spike_D614G, NSP2_I120F, NSP12_P323L, and NSP2_V480I.
Introduction: In BCSIR-NILMRC-008, the genome mutations Spike_D614G, N_R203K, N_G204R, NSP2_
Structural and Functional Analysis of the D614G SARS-CoV-2 Spike Protein Variant.
Result: These four SNPs include C241U in the 5'UTR, a silent mutation C3037U, C14408U encoding the RNA-dependent RNA polymerase variant P323L, and A23403G encoding the spike protein variant D614G.
Experimental and in silico evidence suggests vaccines are unlikely to be affected by D614G mutation in SARS-CoV-2 spike protein.
Method: An additional solvated model of RdRp was built to help as
Result: It is not immediately clear what effect the P323L mutation has on virulence.
Result: Secondly, a parallel C-to-U substitution at position 14,408 in the genome, resulting in a P323L (P314L in orf1b) mutation in the RNA-dependent polymerase (RdRp/nsp12), has been associated with D614G (including in VIC31) and should therefore be considered for potential contribution to infectivity.
Result: The P323L mutation appears to partially obstruct R349 in the cleft.
Result: The Pro323 to Leu mutation may relieve some backbone constraints and contribute local conformational stability.
New Pathways of Mutational Change in SARS-CoV-2 Proteomes Involve Regions of Intrinsic Disorder Important for Virus Replication and Release.
Figure: Examining the SARS-CoV-2 structure in complex with NSP7 and 8 cofactors (PDB entry 6M71) revealed that the P323L mutation sits in an 'interface' region (spanning residues 250-365) between the N-terminal nidovirus-unique NiRAN domain with nucleotidyltransferase activity and the C-terminal polymerase domain that harbors the fingers, palm and thumb subdomains.
D
Discussion: (1) S-protein: As previously reported, our research exploration reveals the active fixation of the D614G mutation of the S-protein of the spike, which we also find has coordinated entropic trends associated with the P323L mutation of the NSP12 polymerase that mediates viral replication (Figure 3).
Genomic exploration light on multiple origin with potential parsimony-informative sites of the severe acute respiratory syndrome coronavirus 2 in Bangladesh.
Abstract: Genome-wide annotations revealed 256 mutations, of which 10 were novel (NSP3, RdRp, Spike) in Bangladeshi strains where I120F(NSP2), P323L(RdRp), D614G (Spike), R203K, G204R(N) are the most prominent.
Discussion: Among the mutations, the most frequent 2 mutations were D614G (Spike protein) and P323L (NSP12).
Genetic diversity of SARS-CoV-2 and clinical, epidemiological characteristics of COVID-19 patients in Hanoi, Vietnam.
Abstract: The three most common variants were linked, and included C3037T, C14408T (nsp12: P323L) and A23403G (S: D614G) mutations.
Result: The most ubiquitous modifications were
Table: P323L
Discussion: We characterised the three most prevalent variants detected in 40/44 completed genome sequences, namely C3037T (synonymous substitution) and two non-synonymous mutations C14408T (nsp12: P323L), A23403G (S: D614G).
SARS_CoV_2 mutation literature information.
PMID: 
2020
bioRxiv
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