Abstract:AbstractSARS-CoV-2 caused a global pandemic in early 2020 and has resulted in more than 8,000,000 infections as well as 430,000 deaths in the world so far. Four structural proteins, envelope (E), membrane (M), nucleocapsid (N) and spike (S) glycoprotein, play a key role in controlling the entry into human cells and virion assembly of SARS-CoV-2. However, how these genes evolve during its human to human transmission is largely unknown. In this study, we screened and analyzed rou… Show more
“…Despite this uniquely high fidelity of replication, a number of mutations to the SARS-CoV-2 genome have been observed throughout the present course of the COVID-19 pandemic, including in the S gene. Indeed, analysis of 3090 isolates in June 2020 found that the number of unique alleles of S was greater than the other structural genes M, N, and E, suggesting that changes in S may provide an evolutionary benefit [ 31 ]. One non-synonymous mutation of S gene in particular, an aspartic acid-to-glycine substitution at amino acid position 614 (D614G), has attracted immense attention following reports of its enrichment discovered by epidemiological surveillance [ 32 ].…”
Section: Introductionmentioning
confidence: 99%
“…Another group observed a similar trend, although not statistically significant in their dataset [ 40 ]. Moreover, computational models of evolutionary dynamics suggest that D614G is under strong selective pressure [ 31 ]. Further, quantitative estimates of the basic reproductive number R 0 from infection incidence data suggest that viruses bearing S(G614) are 31% more transmissible than D614, although this analysis did not consider the effect of concomitant changes at other loci in the circulating viral strains [ 41 ].…”
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an enveloped virus which binds its cellular receptor angiotensin-converting enzyme 2 (ACE2) and enters hosts cells through the action of its spike (S) glycoprotein displayed on the surface of the virion. Compared to the reference strain of SARS-CoV-2, the majority of currently circulating isolates possess an S protein variant characterized by an aspartic acid-to-glycine substitution at amino acid position 614 (D614G). Residue 614 lies outside the receptor binding domain (RBD) and the mutation does not alter the affinity of monomeric S protein for ACE2. However, S(G614), compared to S(D614), mediates more efficient ACE2-mediated transduction of cells by S-pseudotyped vectors and more efficient infection of cells and animals by live SARS-CoV-2. This review summarizes and synthesizes the epidemiological and functional observations of the D614G spike mutation, with focus on the biochemical and cell-biological impact of this mutation and its consequences for S protein function. We further discuss the significance of these recent findings in the context of the current global pandemic.
“…Despite this uniquely high fidelity of replication, a number of mutations to the SARS-CoV-2 genome have been observed throughout the present course of the COVID-19 pandemic, including in the S gene. Indeed, analysis of 3090 isolates in June 2020 found that the number of unique alleles of S was greater than the other structural genes M, N, and E, suggesting that changes in S may provide an evolutionary benefit [ 31 ]. One non-synonymous mutation of S gene in particular, an aspartic acid-to-glycine substitution at amino acid position 614 (D614G), has attracted immense attention following reports of its enrichment discovered by epidemiological surveillance [ 32 ].…”
Section: Introductionmentioning
confidence: 99%
“…Another group observed a similar trend, although not statistically significant in their dataset [ 40 ]. Moreover, computational models of evolutionary dynamics suggest that D614G is under strong selective pressure [ 31 ]. Further, quantitative estimates of the basic reproductive number R 0 from infection incidence data suggest that viruses bearing S(G614) are 31% more transmissible than D614, although this analysis did not consider the effect of concomitant changes at other loci in the circulating viral strains [ 41 ].…”
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an enveloped virus which binds its cellular receptor angiotensin-converting enzyme 2 (ACE2) and enters hosts cells through the action of its spike (S) glycoprotein displayed on the surface of the virion. Compared to the reference strain of SARS-CoV-2, the majority of currently circulating isolates possess an S protein variant characterized by an aspartic acid-to-glycine substitution at amino acid position 614 (D614G). Residue 614 lies outside the receptor binding domain (RBD) and the mutation does not alter the affinity of monomeric S protein for ACE2. However, S(G614), compared to S(D614), mediates more efficient ACE2-mediated transduction of cells by S-pseudotyped vectors and more efficient infection of cells and animals by live SARS-CoV-2. This review summarizes and synthesizes the epidemiological and functional observations of the D614G spike mutation, with focus on the biochemical and cell-biological impact of this mutation and its consequences for S protein function. We further discuss the significance of these recent findings in the context of the current global pandemic.
“…This study also reported that of 250 high coverage complete genome hCoV-19/Malaysia strains deposited in the GISAID database, 114 of the virus strains harboured D614G mutations in Spike protein ( Table 3 ). Altogether, these results suggest the SARS-CoV-2 Malaysia isolate was subjected to intense positive selection pressure [29] and a persistent D614G mutation identified may be responsible for the quick spread of SARS-CoV-2 in Malaysia. Fig.…”
Section: Resultsmentioning
confidence: 87%
“…3 ). Therefore, suggesting Pahang/IIUM91 was not correlated to Sivagangga cluster, which originated from India [29] . Fig.…”
SARS-CoV-2 is a very transmissible and pathogenic coronavirus which detected in Malaysia in January 2020. Nevertheless, the sample from Malaysia is still under-sequenced. Hence lacking clarity of the circulating strain in Malaysia leads to a deadlock in understanding the virus infectivity. This study aimed to investigate the genome identity of circulating COVID-19 strains in Pahang and understand disease epidemiology during the pandemic. This study leveraged high-throughput sequencing analysis for the whole genome sequencing and implemented bioinformatic technique for the analysis. Here we reported that the virus with D614G mutation in Spike protein circulates in a few Malaysia states before the Sivagangga cluster announced in Kedah in July 2020. This mutated virus includes our virus sample isolated in April 2020 from an asymptomatic patient in Pahang. Based on the phylogenetic analysis, we discovered the origin of our sample Pahang/IIUM91 was not related to Sivagangga cluster. Here, we have generated 3D structure model of Pahang/IIUM91 Spike protein. D614G mutation in Pahang/IIUM91 Spike protein increases viral stability and flexibility, hence render higher infectivity. Collectively, our results suggest for the establishment of a complete SARS-CoV-2 genome database in Malaysia. Hence, more research should be established to learn the behaviour of this virus.
“…Further evolution of these spike proteins could enhance binding to human ACE2, enhancing transmission, infection rate, virulence, while exacerbating symptoms. Specific interest has focused on codon 614 of an especially glycosylated region of the viral spike protein, where positive natural selection has been confirmed for the D614G variant [7,12,19].…”
As the SARS-Cov-2 virus spreads around the world afflicting millions of people, it has undergone divergent genetic mutations. Although most of these mutations are expected to be inconsequential, some mutations in the spike protein structure have been hypothesized to affect the critical stage at which the virus invades human cells, which could affect transmission probability and disease expression. If true, then we expect an increased growth rate of reported COVID-19 cases in regions dominated by viruses with these altered proteins. We modeled early global infection dynamics based on clade assignment along with other demographic and meteorological factors previously found to be important. Clade, but not variant D614G which has been associated with increased viral load, enhanced our ability to describe early COVID-19 growth dynamics. Including clade identity in models significantly improved predictions over earlier work based only on weather and demographic variables. In particular, higher proportions of clade 19A and 19B were negatively correlated with COVID-19 growth rate, whereas higher proportions of 20A and 20C were positively correlated with growth rate. A strong interaction between the prevalence of clade 20C and relative humidity suggests that the impact of clade identity might be more important when coupled with certain weather conditions. In particular, 20C an 20A generate the highest growth rates when coupled with low humidity. Projections based on data through April 2020 suggest that, without intervention, COVID-19 has the potential to grow more quickly in regions dominated by the 20A and 20C clades, including most of South and North America.
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