Could the D614G substitution in the SARS-CoV-2 spike (S) protein be associated with higher COVID-19 mortality?

Eaaswarkhanth, Muthukrishnan; Madhoun, Ashraf Al; Al-Mulla, Fahd

doi:10.1016/j.ijid.2020.05.071

Cited by 147 publications

(147 citation statements)

References 6 publications

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“…As previous reported, S68F and P71L nonsynonymous mutation in E-protein of SARS CoV-2 were the most common mutation in in E-protein [22]; Q57H, G251V and G196V non-synonymous mutation in ORF3a of SARS-CoV-2 would link in the virulence, infectivity, ion channel activity and viral release [23]; deletion of ORF8 increased the interferon production and reduced in inflammatory cytokines level [24][25][26]. Most recently, researchers found that D614G non-synonymous mutation located in spike protein would increases infectivity [27][28][29][30].…”

Section: Sars-cov-2 Snvs and Protein Functionsmentioning

confidence: 99%

Genetic spectrum and distinct evolution patterns of SARS-CoV-2

Liu

Shen

Fang

et al. 2020

Preprint

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Four signature groups of single-nucleotide variants (SNVs) were identified using two-way clustering method in about twenty thousand high quality and high coverage SARS-CoV-2 complete genome sequences. Some frequently occurred SNVs predominate but are mutually exclusively presented in patients from different countries and areas. These major SNV signatures exhibited distinguished evolution patterns over time. Although it was rare, our data indicated possible cross-infections with multiple groups of SNVs existed simultaneously in some patients, suggesting infections from different SARS-CoV-2 clades or potential re-combination of SARS-CoV-2 sequences. Interestingly nucleotide substitutions among SARS-CoV-2 genomes tend to occur at the sites where one bat RaTG13 coronavirus sequences differ from Wuhan-Hu-1 genome, indicating the tolerance of mutations on those sites or suggesting that major viral strains might exist between Wuhan-Hu-1 and RaTG13 coronavirus.

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Section: Sars-cov-2 Snvs and Protein Functionsmentioning

confidence: 99%

Genetic spectrum and distinct evolution patterns of SARS-CoV-2

Liu

Shen

Fang

et al. 2020

Preprint

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“…SARS-CoV-2 S variants have been found to be circulating in the human population and it is likely that others are yet to emerge, some of which may be less sensitive to neutralization by the therapeutic monoclonal antibodies currently under development. The recently identified SARS-CoV-2 variant encoding the D614G S protein has been found to be spreading with increased frequency in the human population (Daniloski et al, 2020;Eaaswarkhanth et al, 2020;Korber et al, 2020;Zhang et al, 2020). The D614G S protein was found to be more resistant to shedding from the virion and to adopt a conformation that favors ACE2-binding and is in a more fusioncompetent state (Yurkovetskiy et al, 2020;Zhang et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

“…CoV-2 containing a D614G point mutation in the S protein has been found to be circulating in the human population with increasing prevalence (Daniloski et al, 2020;Eaaswarkhanth et al, 2020;Korber et al, 2020;Zhang et al, 2020). The D614G mutation was found to decrease shedding of the spike protein from the virus and to assume a fusion-ready conformation, resulting in increased infectivity and most likely contributing to its increasing prevalence.…”

Section: Ace2 Microbody Blocks Entry Of Virus With D614g Mutant Spikementioning

confidence: 99%

A soluble ACE2 microbody protein fused to a single immunoglobulin Fc domain is a potent inhibitor of SARS-CoV-2 infection in cell culture

Tada

Chen

Kaur

et al. 2020

Preprint

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SummarySoluble forms of ACE2 have recently been shown to inhibit SARS-CoV-2 infection. We report on an improved soluble ACE2, termed a “microbody” in which the ACE2 ectodomain is fused to Fc domain 3 of the immunoglobulin heavy chain. The protein is smaller than previously described ACE2-Ig Fc fusion proteins and contains an H345A mutation in the ACE2 catalytic active site that inactivates the enzyme without reducing its affinity for the SARS-CoV-2 spike. The disulfide-bonded ACE2 microbody protein inhibited entry of lentiviral SARS-CoV-2 spike protein pseudotyped virus and live SARS-CoV-2 with a potency 10-fold higher than unmodified soluble ACE2 and was active after initial virus binding to the cell. The ACE2 microbody inhibited the entry of ACE2-specific β coronaviruses and viruses with the high infectivity variant D614G spike. The ACE2 microbody may be a valuable therapeutic for COVID-19 that is active against SARS-CoV-2 variants and future coronaviruses that may arise.

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“…5775 mutations in the SARS-CoV-2 genome were discovered from 10022 public genome data assemblies as at May 1, 2020 [9], in which missense mutations of S protein were detected. Among these spike mutations, D614G mutation, in which Aspartic acid (D) was replaced with Glycine (G) at the AA site of 614, was a major mutation of great concern [10,11]. SARS-CoV-2 with D614G mutation may have triggered fatal infections in many European countries, such as Spain, Italy, France, etc.…”

Section: Introductionmentioning

confidence: 99%

“…SARS-CoV-2 with D614G mutation may have triggered fatal infections in many European countries, such as Spain, Italy, France, etc. [11].…”

Section: Introductionmentioning

confidence: 99%

The influence of major S protein mutations of SARS-CoV-2 on the potential B cell epitopes

Yuan

2020

Preprint

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SARS-CoV-2 has rapidly transmitted worldwide and results in the COVID-19 pandemic . Spike glycoprotein on surface is a key factor of viral transmission, and has appeared a lot of variants due to gene mutations, which may influence the viral antigenicity and vaccine efficacy . Here, we used bioinformatic tools to analyze B - cell epitopes of prototype S protein and its 9 common variant s. 12 potential linear and 53 discontinuous epitopes of B-cell s were predicted from the S protein prototype . Importantly, by c omparing the epitope alterations between prototype and variant s, we demonstrate that B-cell epitopes and antigenicity of 9 variant s appear significantly different alterations. The dominant D614 G variant impacts the potential epitope least, o nly with moderately elevated antigenicity , while the epitopes and antigenicity of some mutants ( V483A, V367F , etc.) with small incidence in the population change greatly. These results suggest that t he current ly developed vaccine s should be valid for a majority of SARS-CoV-2 infectors . This study provides a scientific basis for large-scale application of SARS-CoV-2 vaccines and for taking precautions against the probable appearance of antigen escape induced by genetic variation after vaccination .

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Could the D614G substitution in the SARS-CoV-2 spike (S) protein be associated with higher COVID-19 mortality?

Cited by 147 publications

References 6 publications

Genetic spectrum and distinct evolution patterns of SARS-CoV-2

Genetic spectrum and distinct evolution patterns of SARS-CoV-2

A soluble ACE2 microbody protein fused to a single immunoglobulin Fc domain is a potent inhibitor of SARS-CoV-2 infection in cell culture

The influence of major S protein mutations of SARS-CoV-2 on the potential B cell epitopes

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