The D614G mutations in the SARS-CoV-2 spike protein: Implications for viral infectivity, disease severity and vaccine design

Groves, Danielle C.; Rowland‐Jones, Sarah; Angyal, Adrienn

doi:10.1016/j.bbrc.2020.10.109

Cited by 100 publications

(107 citation statements)

References 21 publications

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“…Recently, SARS-CoV-2 isolates with the D614G mutation in the S protein were described [ 13 , 19 - 22 ]. Over a short period of time, those mutant variants have gained dominance in many areas where they were found.…”

Section: Hypothesis and Discussionmentioning

confidence: 99%

“…It was demonstrated that the D614G mutation decreases the stability of the S protein trimer and facilitates RBD transition into its open conformation [ 23 ]. This mutation increases the overall virus infectivity and fitness [ 19 - 22 , 24 ], increases affinity of furin binding to the S protein [ 25 ], and promotes viral replication [ 26 ]. However, there are no indications that the D614G mutation is associated with more severe COVID-19 infection symptoms.…”

Section: Hypothesis and Discussionmentioning

confidence: 99%

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Free SARS-CoV-2 Spike Protein S1 Particles May Play a Role in the Pathogenesis of COVID-19 Infection

Letarov

Babenko

Kulikov

2020

Biochemistry Moscow

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The imbalance of the renin-angiotensin system is currently considered as a potentially important factor of the pathogenesis of COVID-19 disease. It has been shown previously in the murine model, that the expression of angiotensin-converting enzyme 2 (ACE2) on the cell surface is downregulated in response to the infection by SARS-CoV virus or recombinant spike protein (S protein) alone. In the case of natural infection, circulation of the S protein in a soluble form is unlikely. However, in SARS-CoV-2, a large fraction of S protein trimers is pre-processed during virion morphogenesis due to the presence of furin protease cleavage site between the S1 and S2 subunits. Therefore, S protein transition into the fusion conformation may be accompanied by the separation of the S1 subunits carrying the receptor-binding domains from the membrane-bound S2 subunits. The fate of the S1 particles shed due to the spontaneous “firing” of some S protein trimers exposed on the virions and on the surface of infected cells has been never investigated. We hypothesize that the soluble S1 subunits of the SARS-CoV-2 S protein shed from the infected cells and from the virions in vivo may bind to the ACE2 and downregulate cell surface expression of this protein. The decrease in the ACE2 activity on the background of constant or increased ACE activity in the lungs may lead to the prevalence of angiotensin II effects over those of angiotensin (1-7), thus promoting thrombosis, inflammation, and pulmonary damage. This hypothesis also suggests the association between less pronounced shedding of the S1 particles reported for the S protein carrying the D614G mutation (vs. the wild type D614 protein), and lack of increased severity of the COVID-19 infection caused by the mutant (D614G) SARS-CoV-2 strain, despite its higher infectivity and higher in vivo viral load.

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Section: Hypothesis and Discussionmentioning

confidence: 99%

Section: Hypothesis and Discussionmentioning

confidence: 99%

Free SARS-CoV-2 Spike Protein S1 Particles May Play a Role in the Pathogenesis of COVID-19 Infection

Letarov

Babenko

Kulikov

2020

Biochemistry Moscow

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“…For example, the common mutation D614G on the S protein may increase binding affinity between the S protein and host ACE2 receptor, thus enhancing virus loads which lead to increased infectivity. Although the mutation does not change the ability of antibody recognition, the G-form variant is more readily neutralized by a human antibody [33] . By investigating 80 mutants and 26 modifications of the glycosylation site on the S protein, Li et al [34] found that several mutants, including A475V, L452R, V483A, and F490L increased their resistance to neutralizing antibodies and deletion of glycosylation sites N331 and N343 decreased viral infectivity.…”

Section: Genetic Mutations Of Sars-cov-2mentioning

confidence: 96%

Biochemical features and mutations of key proteins in SARS-CoV-2 and their impacts on RNA therapeutics

Zeng

Tong

et al. 2021

Biochemical Pharmacology

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“…Structure and function (genomic/proteomic) comparison of nsp14 and nsp10 (independently and in complex) between sister clades of SARS-CoV-2 variants (D614G 488,489 , N501Y 490 , etc. 491 ) may offer clues, if we can identify specific mutations in the parent genome which affected nsp14 (exoribonuclease for proofreading) and/or nsp10, resulting in progeny which causes more harm.…”

Section: Appendix IV -Aptamers As Adjuvants And/or Parallel Alternatimentioning

confidence: 99%

Aptamers for Detection and Diagnostics (ADD) is a proposed mobile app acquiring optical data from conjugated quantum nanodots to identify molecules indicating presence of SARS-CoV-2 virus: Why public health and healthcare need smartphone sensors as a platform for early detection and prevention

Datta

2021

Preprint

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Proposed SARS-CoV-2 surveillance tool using a mobile app for non-invasive monitoring of humans and animals. <p>Engineering a biomedical device as a low-cost, non-invasive, detection, and diagnostic platform for surveillance of infections in humans, and animals. The system embraces the IoT <i>“digital by design”</i> metaphor by incorporating elements of connectivity, data sharing and (secure) information arbitrage. Using an array of aptamers to bind viral targets may help in detection, diagnostics, and potentially prevention in case of SARS-CoV-2. The ADD tool may become part of a broader platform approach.</p>

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The D614G mutations in the SARS-CoV-2 spike protein: Implications for viral infectivity, disease severity and vaccine design

Cited by 100 publications

References 21 publications

Free SARS-CoV-2 Spike Protein S1 Particles May Play a Role in the Pathogenesis of COVID-19 Infection

Free SARS-CoV-2 Spike Protein S1 Particles May Play a Role in the Pathogenesis of COVID-19 Infection

Biochemical features and mutations of key proteins in SARS-CoV-2 and their impacts on RNA therapeutics

Aptamers for Detection and Diagnostics (ADD) is a proposed mobile app acquiring optical data from conjugated quantum nanodots to identify molecules indicating presence of SARS-CoV-2 virus: Why public health and healthcare need smartphone sensors as a platform for early detection and prevention

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