SARS-CoV-2 spike-protein D614G mutation increases virion spike density and infectivity

Zhang, Lizhou; Jackson, Cody B.; Mou, Huihui; Ojha, Amrita; Peng, Haiyong; Quinlan, Brian D.; Rangarajan, Erumbi S.; Pan, Andi; Vanderheiden, Abigail; Suthar, Mehul S.; Li, Wenhui; Izard, Tina; Rader, Christoph; Farzan, Michael; Choe, Hyeryun

doi:10.1038/s41467-020-19808-4

Cited by 970 publications

(1,028 citation statements)

References 42 publications

(67 reference statements)

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“…Additionally, it is important to note that the usefulness of D-dimer in the management of patients with COVID-19 remains uncertain [ 18 ]. Moreover, we report here only a single case, yet several mutations in SARS-CoV-2 have been reported, in which the pathogenicity of the virus may differ [ 19 ]. To verify the accuracy of the change in serum SDC-1 level in COVID-19 patients, further large-scale studies are warranted.…”

Section: Resultsmentioning

confidence: 99%

Possible involvement of Syndecan-1 in the state of COVID-19 related to endothelial injury

et al. 2021

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Background The coronavirus infection 2019 (COVID-19) is associated with microvascular endothelial injury. Here, we report that syndecan-1, a component of endothelial glycocalyx, may reflect the disease state of COVID-19 related to endothelial injury. Case presentation A patient with COVID-19 was transferred to the intensive care unit of our hospital. Computed tomography of the chest showed bilateral ground glass opacities, which was diagnosed as acute respiratory syndrome. The PaO2/FIO2 ratio gradually increased from 158 on hospitalization to 300 on Day 11, on which day the ventilator was withdrawn. However, serum syndecan-1 (SDC-1) level gradually decreased from 400.5 ng/ml at hospitalization to 165.1 ng/ml on Day 5. On Day 6, serum SDC-1 level increased to 612.9 ng/ml owing to a systemic thrombosis with an increase in D-dimer. Serum SDC-1 level then decreased until 206.0 ng/ml on Day 11 after a decrease in D-dimer. The patient was transferred to another hospital on Day 21 after hospitalization. Conclusions In this case report, changes in serum SDC-1 level closely reflected the change in disease condition in a patient with COVID-19. Serum SDC-1 may be a useful biomarker for monitoring the disease state of critically ill patients with COVID-19.

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Section: Resultsmentioning

confidence: 99%

Possible involvement of Syndecan-1 in the state of COVID-19 related to endothelial injury

et al. 2021

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“…In our study, the D614G polymorphism that has become globally dominant in humans was not detected. This polymorphism has been associated with increased virus entry into host cells [ 50 ] and infectivity [ 51 ]. In the hamster model, the D614G mutation significantly accelerated droplet transmission during the initial stages of infection [ 52 ], whilst in ferrets, it provided an advantage for viral replication and transmission but did not alter pathogenicity [ 53 ].…”

Section: Discussionmentioning

confidence: 99%

Intranasal Infection of Ferrets with SARS-CoV-2 as a Model for Asymptomatic Human Infection

Everett

Lean

Byrne

et al. 2021

Viruses

101

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Ferrets were experimentally inoculated with SARS-CoV-2 (severe acute respiratory syndrome (SARS)-related coronavirus 2) to assess infection dynamics and host response. During the resulting subclinical infection, viral RNA was monitored between 2 and 21 days post-inoculation (dpi), and reached a peak in the upper respiratory cavity between 4 and 6 dpi. Viral genomic sequence analysis in samples from three animals identified the Y453F nucleotide substitution relative to the inoculum. Viral RNA was also detected in environmental samples, specifically in swabs of ferret fur. Microscopy analysis revealed viral protein and RNA in upper respiratory tract tissues, notably in cells of the respiratory and olfactory mucosae of the nasal turbinates, including olfactory neuronal cells. Antibody responses to the spike and nucleoprotein were detected from 21 dpi, but virus-neutralizing activity was low. A second intranasal inoculation (re-exposure) of two ferrets after a 17-day interval did not produce re-initiation of viral RNA shedding, but did amplify the humoral response in one animal. Therefore, ferrets can be experimentally infected with SARS-CoV-2 to model human asymptomatic infection.

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“…A molecular virological study investigated the details of conformational changes between D614 and G614 variants, and showed that the D614G mutation shifts the S glycoprotein conformation to be more open, which could contribute to the increased efficiency of ACE2 binding and fusion [ 10 ]. The SARS-CoV-2 D614G mutation notably did not increase the binding affinity with ACE2 [ 9 , 11 ].…”

Section: Discussionmentioning

confidence: 99%

“…One of the predominant mutations, D614G, is located in the spike (S) glycoprotein in SARS-CoV-2 and was found by a current study to display increased virulence [ 9 , 10 , 11 , 12 , 13 ]. This mutation was not detected during the early pandemic, but became prominent outside China [ 9 ]. The most important receptor for the SARS-CoV-2 S glycoprotein was identified as angiotensin 1-converting enzyme 2 (ACE2).…”

Section: Introductionmentioning

confidence: 91%

“…The D614G mutation in the S glycoprotein can affect SARS-CoV-2 infectivity by affecting the RBD structure, S1/S2 subunit interaction, viral entry, and immune response [ 12 ]. A molecular virology study by Zhang and colleagues showed that the D614G mutation in the SARS-CoV-2 S glycoprotein can decrease S1 shedding and increase S glycoprotein incorporation into the virion, thereby enhancing SARS-CoV-2 infectivity [ 9 ]. However, according to a recent study, whether more S glycoprotein is incorporated into the SARS-CoV-2 D614G virion is still controversial [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

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Impact of Genetic Variability in ACE2 Expression on the Evolutionary Dynamics of SARS-CoV-2 Spike D614G Mutation

Huang

Miller

Yen

et al. 2020

Genes

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The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) glycoprotein D614G mutation became the predominant globally circulating variant after its emergence in the early coronavirus disease 2019 (COVID-19) pandemic. Studies showed that this mutation results in an open conformation of the S glycoprotein receptor-binding domain (RBD), and increased angiotensin 1-converting enzyme 2 (ACE2) binding and fusion, which result in an increase in SARS-CoV-2 transmissibility and infectivity. Dynamic tracking of SARS-CoV-2 showed that the D614G variant became predominant after emergence in Europe and North America, but not in China. The current absence of selective pressures from antiviral treatment suggests that the driving force for viral evolution could be variations in human population genetics. Results show that ACE2 expression is higher in Asian populations than that in European, North American, and African populations. This supports the idea that lower ACE2 expression is a driving force in the positive selection for the D614G mutation. This study suggests that the dynamics of the SARS-CoV-2 D614G mutation during the early-to-mid pandemic is associated with enhanced transmission efficiency in populations with lower ACE2 expression. Understanding the role that human genetic diversity plays in the adaptive evolution of SARS-CoV-2 may have an important impact on public health and measures to control the pandemic.

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SARS-CoV-2 spike-protein D614G mutation increases virion spike density and infectivity

Cited by 970 publications

References 42 publications

Possible involvement of Syndecan-1 in the state of COVID-19 related to endothelial injury

Possible involvement of Syndecan-1 in the state of COVID-19 related to endothelial injury

Intranasal Infection of Ferrets with SARS-CoV-2 as a Model for Asymptomatic Human Infection

Impact of Genetic Variability in ACE2 Expression on the Evolutionary Dynamics of SARS-CoV-2 Spike D614G Mutation

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