Quantitative Characterization and Prediction of the Binding Determinants and Immune Escape Hotspots for Groups of Broadly Neutralizing Antibodies Against Omicron Variants: Atomistic Modeling of the SARS-CoV-2 Spike Complexes with Antibodies DOI Open Access
Mohammed Alshahrani, Victoria N. Parikh, Brian Foley

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 20, 2024

Abstract The growing body of experimental and computational studies suggested that the cross-neutralization antibody activity against Omicron variants may be driven by balance tradeoff multiple energetic factors interaction contributions evolving escape hotspots involved in antigenic drift convergent evolution. However, dynamic details quantifying contribution these factors, particularly balancing nature specific interactions formed antibodies with epitope residues remain scarcely characterized. In this study, we performed molecular dynamics simulations, ensemble-based deep mutational scanning SARS-CoV-2 spike binding free energy computations for two distinct groups broadly neutralizing : E1 group (BD55-3152, BD55-3546 BD5-5840) F3 (BD55-3372, BD55-4637 BD55-5514). Using approaches, examine determinants which potent can largely evade immune resistance. Our analysis revealed emergence a small number positions correspond to R346 K444 strong van der Waals act synchronously leading large contribution. According our results, Abs effectively exploit hotspot clusters hydrophobic sites critical functions along selective complementary targeting positively charged are important ACE2 binding. Together conserved epitopes, lead expanded neutralization breadth resilience shift associated viral results study demonstrate excellent qualitative agreement between predicted mutations respect latest experiments on average scores. We argue epitopes leverage stability binding, while tend emerge synergistically electrostatic interactions.

Language: Английский

Reviewer response for version 1 DOI Creative Commons
Samuel Wilkinson

Published: June 12, 2024

During the three years following emergence of COVID-19 pandemic, African continent, like other regions world, was significantly impacted by COVID-19. In Morocco, pandemic has been marked and spread several SARS-CoV-2 variants, leading to a substantial increase in incidence infections deaths. Nevertheless, there persistent lack comprehensive understanding regarding genetic diversity, evolution, epidemiology viral lineages. The aim this study analyze diversity identify distinct lineages, as well assess their evolution during using genomic approaches. Furthermore, key mutations functional proteins across different lineages were highlighted along with an analysis relationships amongst these strains better understand evolutionary pathways. A total 2274 sequences SARS-CoV-2, acquired from Morocco period 2020 2023, extracted GISAID EpiCoV database subjected analysis. Lineages clades classified according nomenclature GISAID, Nextstrain, Pangolin. conducted reported accordance STROBE (Strengthening Reporting Observational Studies Epidemiology) guidelines. An exhaustive led identification 157 PANGO including notable such B.1, B.1.1, B.1.528 B.1.177, variants B.1.1.7, B.1.621, B.1.525, B.1.351, B.1.617.1, B.1.617.2 its sub-lineages AY.33, AY.72, AY.112, AY.121 that evolved over time before being supplanted Omicron December 2021. Among analyzed, sub-variants had prevalence 59.5%. most predominant 21K, 21L, 22B, which are respectively related phylogenetically BA.1, BA.2, BA.5. June 2022, rapidly observed recrudescence cases infection, concurrent coexistence subvariants clade 22B BA.5.2.20, BA.5, BA.5.1, BA.5.2.1, BF.5, supplanting BA.1 (Clade display 21K) BA.2 21L), became marginal. However, XBB (clade 22F) progeny XBB.1.5(23A), XBB.1.16(23B), CH.1.1(23C), XBB.1.9(23D), XBB.2.3(23E), EG.5.1(23F), XBB.1.5.70 (23G) have sporadically. mutations, H69del/V70del, G142D, K417N, T478K, E484K, E484A, L452R, F486P, N501Y, Q613H, D614G, P681H/R, known for implications transmissibility infectivity ability escape antibodies, identified. This identified various involved Moroccan isolates, analyzed trends. genetically closely linked original highlighting importance maintaining continuous surveillance extending vaccination coverage prevent new could potentially be more infectious. These findings also provide robust basis role transmission, immune evasion, reinfection.

Language: Английский

Citations

0

Editor response for version 2 DOI Creative Commons
Rebecca A. Hall

Published: July 24, 2024

During the three years following emergence of COVID-19 pandemic, African continent, like other regions world, was substantially impacted by COVID-19. In Morocco, pandemic has been marked and spread several SARS-CoV-2 variants, leading to a substantial increase in incidence infections deaths. Nevertheless, there persistent lack comprehensive understanding regarding genetic diversity, evolution, epidemiology viral lineages. This study sought deepen genomic through retrospective analysis.The main objective this analyze diversity identify distinct lineages, as well assess their evolution during using approaches.Furthermore, key mutations functional proteins across different lineages were highlighted along with an analysis relationships amongst these strains better understand evolutionary pathways. A total 2274 sequences SARS-CoV-2, acquired from Morocco period 2020 2023, extracted GISAID EpiCoV database subjected analysis. Lineages clades classified according nomenclature GISAID, Nextstrain, Pangolin. The conducted reported accordance STROBE (Strengthening Reporting Observational Studies Epidemiology) guidelines. An exhaustive led identification 157 PANGO including notable such B.1, B.1.1, B.1.528 B.1.177, variants B.1.1.7, B.1.621, B.1.525, B.1.351, B.1.617.1, B.1.617.2 its sub-lineages AY.33, AY.72, AY.112, AY.121 that evolved over time before being supplanted Omicron December 2021. Among analyzed, sub-variants had prevalence 59.5%. most predominant 21K, 21L, 22B, which are respectively related phylogenetically BA.1, BA.2, BA.5. June 2022, rapidly observed recrudescence cases infection, concurrent coexistence subvariants clade 22B BA.5.2.20, BA.5, BA.5.1, BA.5.2.1, BF.5, supplanting BA.1 (Clade display 21K) BA.2 21L), became marginal. However, XBB (clade 22F) progeny XBB.1.5(23A), XBB.1.16(23B), CH.1.1(23C), XBB.1.9(23D), XBB.2.3(23E), EG.5.1(23F), XBB.1.5.70 (23G) have sporadically. Furthermore, mutations, H69del/V70del, G142D, K417N, T478K, E484K, E484A, L452R, F486P, N501Y, Q613H, D614G, P681H/R, known for implications transmissibility infectivity ability escape antibodies, identified. identified various involved Moroccan isolates, analyzed trends. genetically closely linked original highlighting importance maintaining continuous surveillance expansion vaccine coverage would help protect patients against more severe clinical disease. These findings also provide robust basis role transmission, immune evasion, reinfection.

Language: Английский

Citations

0

Editor response for version 1 DOI Creative Commons
Rubén de Dios

Published: Nov. 18, 2024

The Omicron variant of SARS-CoV-2, which is a cause concern, has various mutations in its spike protein. This protein responsible for both viral infection and immunity. We have analyzed particular sub-lineage Omicron, designated XBB, undergone structural functional changes as response to the African selection pressures. Using molecular modeling, we compared S structures XBB discovered that reduced receptor-binding domain (RBD) because loss some β-sheets. change may result an increased affinity towards human angiotensin-converting enzyme 2 (hACE2) receptor. also conducted recombination analysis sequences using Fast Unconstrained Bayesian Approximation (FUBAR) Recombination Detection Program 4 (RDP 4). Our detected signals positive N-terminal (NTD) S1 subunit, contains antibody-binding epitopes, RBD, involved entry. findings reveal adaptation Africa potential implications pathogenesis

Language: Английский

Citations

0

Assessing the role of deep eutectic solvents in Yarrowia lipolytica inhibition DOI
Filipe Smith Buarque, Bernardo Dias Ribeiro, Mara G. Freire

et al.

Journal of Biotechnology, Journal Year: 2024, Volume and Issue: 398, P. 1 - 10

Published: Nov. 28, 2024

Language: Английский

Citations

0

Quantitative Characterization and Prediction of the Binding Determinants and Immune Escape Hotspots for Groups of Broadly Neutralizing Antibodies Against Omicron Variants: Atomistic Modeling of the SARS-CoV-2 Spike Complexes with Antibodies DOI Open Access
Mohammed Alshahrani, Victoria N. Parikh, Brian Foley

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 20, 2024

Abstract The growing body of experimental and computational studies suggested that the cross-neutralization antibody activity against Omicron variants may be driven by balance tradeoff multiple energetic factors interaction contributions evolving escape hotspots involved in antigenic drift convergent evolution. However, dynamic details quantifying contribution these factors, particularly balancing nature specific interactions formed antibodies with epitope residues remain scarcely characterized. In this study, we performed molecular dynamics simulations, ensemble-based deep mutational scanning SARS-CoV-2 spike binding free energy computations for two distinct groups broadly neutralizing : E1 group (BD55-3152, BD55-3546 BD5-5840) F3 (BD55-3372, BD55-4637 BD55-5514). Using approaches, examine determinants which potent can largely evade immune resistance. Our analysis revealed emergence a small number positions correspond to R346 K444 strong van der Waals act synchronously leading large contribution. According our results, Abs effectively exploit hotspot clusters hydrophobic sites critical functions along selective complementary targeting positively charged are important ACE2 binding. Together conserved epitopes, lead expanded neutralization breadth resilience shift associated viral results study demonstrate excellent qualitative agreement between predicted mutations respect latest experiments on average scores. We argue epitopes leverage stability binding, while tend emerge synergistically electrostatic interactions.

Language: Английский

Citations

0