SARS-CoV-2 Variants Associated with Vaccine Breakthrough in the Delaware Valley through Summer 2021 DOI Creative Commons
Andrew D. Marques, Scott Sherrill-Mix, J.K. Everett

et al.

mBio, Journal Year: 2022, Volume and Issue: 13(1)

Published: Feb. 8, 2022

The severe acute respiratory coronavirus-2 (SARS-CoV-2) is the cause of global outbreak COVID-19. Evidence suggests that virus evolving to allow efficient spread through human population, including vaccinated individuals. Here, we report a study viral variants from surveillance Delaware Valley, city Philadelphia, and infecting subjects. We sequenced analyzed complete genomes 2621 samples March 2020 September 2021 compared them genome sequences 159 vaccine breakthroughs. In early spring 2020, all detected were B.1 closely related lineages. A mixture lineages followed, notably B.1.243 followed by B.1.1.7 (alpha), with other present at lower levels. Later isolations dominated B.1.617.2 (delta) delta lineages; was exclusive variant last time sampled. To investigate whether any appeared preferentially in breakthroughs, devised model based on Bayesian autoregressive moving average logistic multinomial regression rigorous comparison. This revealed showed 3-fold enrichment breakthrough cases (odds ratio 3; 95% credible interval 0.89-11). Viral point substitutions could also be associated N501Y substitution found alpha, beta gamma 2.04; of1.25-3.18). thus overviews evolution breakthroughs Valley introduces statistical approach interrogating against changing background.

Language: Английский

Some mechanistic underpinnings of molecular adaptations of SARS-COV-2 spike protein by integrating candidate adaptive polymorphisms with protein dynamics DOI Creative Commons
Nicholas J. Ose, Paul Campitelli, Tushar Modi

et al.

eLife, Journal Year: 2024, Volume and Issue: 12

Published: May 7, 2024

We integrate evolutionary predictions based on the neutral theory of molecular evolution with protein dynamics to generate mechanistic insight into adaptations SARS-COV-2 spike (S) protein. With this approach, we first identified candidate adaptive polymorphisms (CAPs) SARS-CoV-2 S and assessed impact these CAPs through analysis. Not only have found that frequently overlap well-known functional sites, but also, using several different dynamics-based metrics, reveal critical allosteric interplay between binding sites human ACE2 (hACE2) interact far differently hACE2 site residues in open conformation compared closed form. In particular, CAP control state, suggesting an binding. also explored characteristic mutations strains find dynamic hallmarks potential effects future mutations. Our analyses Delta strain-specific variants non-additive (i.e., epistatic) interactions whereas less pathogenic Omicron mostly additive Finally, our analysis suggests novel observed strain epistatically help escape antibody

Language: Английский

Citations

4
SARS-CoV-2 spike conformation determines plasma neutralizing activity DOI Creative Commons
John E. Bowen, Alexandra C. Walls,

Anshu Joshi

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2021, Volume and Issue: unknown

Published: Dec. 21, 2021

Numerous safe and effective COVID-19 vaccines have been developed that utilize various delivery technologies engineering strategies. The influence of the SARS-CoV-2 spike (S) glycoprotein conformation on antibody responses induced by vaccination or infection in humans remains unknown. To address this question, we compared plasma antibodies elicited six globally-distributed observed markedly higher binding titers for encoding a prefusion-stabilized S relative to other groups. Prefusion positively correlated with neutralizing activity, indicating physical stabilization prefusion enhances protection against SARS-CoV-2. We show almost all activity is directed S, particular

Language: Английский

Citations

25
Ecological and evolutionary dynamics of multi-strain RNA viruses DOI Open Access
Dennis N. Makau, Samantha Lycett, Matthew J. Smith

et al.

Nature Ecology & Evolution, Journal Year: 2022, Volume and Issue: 6(10), P. 1414 - 1422

Published: Sept. 22, 2022

Language: Английский

Citations

18
Dynamic Allostery: Evolution’s Double-Edged Sword in Protein Function and Disease DOI
Paul Campitelli, I. Can Kazan, Sean Hamilton

et al.

Journal of Molecular Biology, Journal Year: 2025, Volume and Issue: unknown, P. 169175 - 169175

Published: April 1, 2025

Language: Английский

Citations

0
SARS-CoV-2 Variants Associated with Vaccine Breakthrough in the Delaware Valley through Summer 2021 DOI Creative Commons
Andrew D. Marques, Scott Sherrill-Mix, J.K. Everett

et al.

mBio, Journal Year: 2022, Volume and Issue: 13(1)

Published: Feb. 8, 2022

The severe acute respiratory coronavirus-2 (SARS-CoV-2) is the cause of global outbreak COVID-19. Evidence suggests that virus evolving to allow efficient spread through human population, including vaccinated individuals. Here, we report a study viral variants from surveillance Delaware Valley, city Philadelphia, and infecting subjects. We sequenced analyzed complete genomes 2621 samples March 2020 September 2021 compared them genome sequences 159 vaccine breakthroughs. In early spring 2020, all detected were B.1 closely related lineages. A mixture lineages followed, notably B.1.243 followed by B.1.1.7 (alpha), with other present at lower levels. Later isolations dominated B.1.617.2 (delta) delta lineages; was exclusive variant last time sampled. To investigate whether any appeared preferentially in breakthroughs, devised model based on Bayesian autoregressive moving average logistic multinomial regression rigorous comparison. This revealed showed 3-fold enrichment breakthrough cases (odds ratio 3; 95% credible interval 0.89-11). Viral point substitutions could also be associated N501Y substitution found alpha, beta gamma 2.04; of1.25-3.18). thus overviews evolution breakthroughs Valley introduces statistical approach interrogating against changing background.

Language: Английский

Citations

16