Abstract: Our analysis allowed also the detection, for the first time in Brazil, the South African B.1.351 (beta) variant of concern, B.1.351 (501Y.V2) (0.5%), characterized by the following mutations: ORF1ab: T265I, R724K, S1612L, K1655N, K3353R, SGF 3675_F3677del, P4715L, E5585D; spike: D80A, D215G, L242_L244del, A262D, K417N, E484K, N501Y, D614G, A701V, C1247F
Evolutionary Tracking of SARS-CoV-2 Genetic Variants Highlights an Intricate Balance of Stabilizing and Destabilizing Mutations.
Result: Two mutations have become consensus: D614G in S (nucleotide 23,403, A to G) and P323L (also known as P4715L) in nsp12 (nucleotide 14,143, C to T).
High Prevalence of SARS-CoV-2 Genetic Variation and D614G Mutation in Pediatric Patients With COVID-19.
PMID: 34095334
2021
Open forum infectious diseases
Result: There were 2 other mutations that coexist with the D614G mutation in all isolates located in ORF1ab: F924F (c.2772C > T) is a synonymous mutation, while P4715L (c.14144C > T) is a nonsynonymous mutation (Figure 3B).
Discussion: ORF1ab P4715L is located in Nsp12, which is important for viral replication.
Discussion: A comprehensive analysis of >12 300 SARS-CoV-2 genome sequences across 28 countries reported that mutation at P4715L and D614G may correlate with higher fatality rates.
Discussion: We also identified the 2 common mutations ( PMID: 33976134
2021
Nature communications
Result: Spike-protein D614G was nearly always co-inherited with RdRp P4715L (also radical and altering a perfectly conserved residue in a highly conserved context, but potentially deleterious given RdRp's slow evolution and less-likely-to-be-adaptive function), nsp3 nucleotide change C3037T (repeatedly observed synonymous change, outside synonymously constrained elements, likely neutral), and nucleotide change C241T (perfectly conserved, non-coding, in a loop of six unpaired bases in the conserved 5'-UTR SL5B secondary structure 25 nucleotides upstream of ORF1a).
Multilevel systems biology analysis of lung transcriptomics data identifies key miRNAs and potential miRNA target genes for SARS-CoV-2 infection.
PMID: 34157472
2021
Computers in biology and medicine
Abstract: All SARS-CoV-2 strains showed a high genetic similarity with the parent Wuhan strain, but Saudi Arabian, South African, USA, Russia and New Zealand strains carry 3 additional genetic variations like P333L (RNA -dependant RNA polymerase), D614G (spike), and P4715L (ORF1ab).
Result: Interestingly, the viral strains from Saudi Arabia, South Africa, USA, Russia and New Zealand have 3 genetic variations:
Discussion: Almost all viral strains with D614G, have also accumulated other variants like P333L (RNA-dependent RNA polymerase) and P4715L (ORF1ab) in proteins responsible for SARS-CoV-2 replication.
Introduction and Characteristics of SARS-CoV-2 in North-East of Romania During the First COVID-19 Outbreak.
Discussion: This mutation is associated with less shedding of S1 subdomain of the S protein, increased viral stability and transmission, although not necessarily with increased disease severity, while other studies associated 614 D > G and 4715 P > L with increased mortality.
Conformational Variability Correlation Prediction of Transmissibility and Neutralization Escape Ability for Multiple Mutation SARS-CoV-2 Strains using SSSCPreds.
Introduction: After March 2020, only two mutations, RNA-directed RNA polymerase P323L (ORF1ab P4715L, ORF1b P314L) and spike protein D614G had nearly overwhelmed the original mutation sites ().
Molecular characterization of SARS-CoV-2 from Bangladesh: implications in genetic diversity, possible origin of the virus, and functional significance of the mutations.
Result: The P4715L, one of the highest frequent SNVs, occurred in the RNA dependent RNA polymerase (RdRp) region of ORF1ab polyprotein.
Discussion: Those mutations include 3037C>T (98%), 14408C>T (98%) and 23403A>G (97%) where the last two are non-synonymous mutations (P4715L in ORF1ab or P323L in RdRp and D614G in Spike protein).
Higher entropy observed in SARS-CoV-2 genomes from the first COVID-19 wave in Pakistan.
Discussion: P4715L and D614G containing isolates have shown significant positive correlations with fatality rates in many countries.
Discussion: The Discussion: The frequency of P4715L has been shown to differ between SARS-CoV-2 genomes isolated from the USA (63.0%) and China (11.2%) and have been attributed to the differential efficacy observed in the clinical trials of the antiviral agent Remdesivir.
Discussion: The most common non-synonymous variants observed were S D614G, Orf1ab RdRp gene P4715L and, Orf3a Q57H which have previously been reported from Europe and the United States.
Mutation in a SARS-CoV-2 Haplotype from Sub-Antarctic Chile Reveals New Insights into the Spike's Dynamics.
Result: Four mutations were located within nonstructural proteins (Nsp3: T1246I, Nsp3: T1250I, Nsp5: G3278S, Nsp12: P4715L), three in the nucleocapsid (S2F, R203K, G204R), and two affecting the spike protein (D614G, T307I) (Figure 3).