SARS‐CoV‐2 viral spike G614 mutation exhibits higher case fatality rate

Becerra-Flores, Manuel; Cardozo, Timothy

doi:10.1111/ijcp.13525

“…To date, the Mexican population is circulating two of three viral lineages reported 10 . The principal mutations detected worldwide in the SARS-CoV-2 are on the viral S protein 9,[11][12][13][14] , which is critical for the virus attachment to the host cell 11 . However, the mutation effects on the S protein are poorly understood and possible impact at 3D structural or functional level.…”

Section: Introductionmentioning

confidence: 99%

Structural insights into spike protein and its natural variants of SARS-CoV-2 found on Mexican population.

Sixto-López

¹

,

Bello

²

,

Correa-Basurto

³

et al. 2020

Preprint

1

0

View full text Add to dashboard Cite

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a newly emerged coronavirus responsible for COVID-19; it becomes a pandemic since March 2020. To date, there are described three lineages of SARS-CoV-2 circulating worldwide, in Mexican population are found two of them, within this, we observed three variants of Spike (S) protein located at H49Y, D614G, and T573I. In order to understand if these mutations could affect the structural behavior of S protein of SARS-CoV-2, as well as the binding with three experimental describe inhibitors (Cepharanthine, Nelfinavir, and Hydroxychloroquine), molecular dynamic simulation and molecular docking were employed. It was found that in spite, these punctual mutations affect considerably the structural behavior of the S Protein, which also affect the binding of the inhibitors into their respective binding site. Thus, further experimental studies need to be done in order to explore if these affectations have an impact on drug-S protein binding and the possible clinical effect.

show abstract

“…Indeed, the D → G mutation at amino acid position 614 in the Spike protein found in our analysis has recently been proposed to have increased viral infectivity [37]. In addition, this same mutation has also been associated with an increase in the case fatality rate [6], however, these hypotheses need further verification. The P323L mutation in the RNA-dependent RNA polymerase (RdRP) has been identified previously, although in that study it was associated with changes in geographical location of the viral strain [56].…”

Section: /24mentioning

confidence: 60%

Genome-wide bioinformatic analyses predict key host and viral factors in SARS-CoV-2 pathogenesis

Ferrarini

¹

,

A

²

,

Rebollo

³

et al. 2020

Preprint

View full text Add to dashboard Cite

The novel betacoronavirus named Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) caused a worldwide pandemic (COVID-19) after initially emerging in Wuhan, China. Here we applied a novel, comprehensive bioinformatic strategy to public RNA sequencing and viral genome sequencing data, to better understand how SARS-CoV-2 interacts with human cells. To our knowledge, this is the first meta-analysis to predict host factors that play a specific role in SARS-CoV-2 pathogenesis, distinct from other respiratory viruses. We identified differentially expressed genes, isoforms and transposable element families specifically altered in SARS-CoV-2 infected cells. Well-known immunoregulators including CSF2, IL-32, IL-6 and SERPINA3 were differentially expressed, while immunoregulatory transposable element families were overexpressed. We predicted conserved interactions between the SARS-CoV-2 genome and human RNA-binding proteins such as hnRNPA1, PABPC1 and eIF4b, which may play important roles in the viral life cycle. We also detected four viral sequence variants in the spike, polymerase, and nonstructural proteins that correlate with severity of COVID-19. The host factors we identified likely represent important mechanisms in the disease profile of this pathogen, and could be targeted by prophylactics and/or therapeutics against SARS-CoV-2.

show abstract

“…Indeed, the D → G mutation at amino acid position 614 in the Spike protein found in our analysis has recently been proposed to have increased viral infectivity [38]. In addition, this same mutation has also been associated with an increase in the case fatality rate [6], however, these hypotheses need further verification. The P323L mutation in the RNA-dependent RNA polymerase (RdRP) has been identified previously, although in that study it was associated with changes in geographical location of the viral strain [58].…”

Section: Dnamentioning

confidence: 60%

Genome-wide bioinformatic analyses predict key host and viral factors in SARS-CoV-2 pathogenesis

Ferrarini¹,

A²,

Rebollo³

et al. 2020

Preprint

View full text Add to dashboard Cite

The novel betacoronavirus named Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) caused a worldwide pandemic (COVID-19) after initially emerging in Wuhan, China. Here we applied a novel, comprehensive bioinformatic strategy to public RNA sequencing and viral genome sequencing data, to better understand how SARS-CoV-2 interacts with human cells. To our knowledge, this is the first meta-analysis to predict host factors that play a specific role in SARS-CoV-2 pathogenesis, distinct from other respiratory viruses. We identified differentially expressed genes, isoforms and transposable element families specifically altered in SARS-CoV-2 infected cells. Well-known immunoregulators including CSF2, IL-32, IL-6 and SERPINA3 were differentially expressed, while immunoregulatory transposable element families were overexpressed. We predicted conserved interactions between the SARS-CoV-2 genome and human RNA-binding proteins such as hnRNPA1, PABPC1 and eIF4b, which may play important roles in the viral life cycle. We also detected four viral sequence variants in the spike, polymerase, and nonstructural proteins that correlate with severity of COVID-19. The host factors we identified likely represent important mechanisms in the disease profile of this pathogen, and could be targeted by prophylactics and/or therapeutics against SARS-CoV-2.

show abstract

SARS‐CoV‐2 viral spike G614 mutation exhibits higher case fatality rate

Cited by 304 publications

References 10 publications

Structural insights into spike protein and its natural variants of SARS-CoV-2 found on Mexican population.

Structural insights into spike protein and its natural variants of SARS-CoV-2 found on Mexican population.

Genome-wide bioinformatic analyses predict key host and viral factors in SARS-CoV-2 pathogenesis

Genome-wide bioinformatic analyses predict key host and viral factors in SARS-CoV-2 pathogenesis

Contact Info

Product

Resources

About