Changes in total charge on spike protein of SARS-CoV-2 in emerging lineages DOI Creative Commons
Anže Božič, Rudolf Podgornik

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Oct. 23, 2023

Motivation: Charged amino acid residues on the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been shown to influence its binding different cell surface receptors, non-specific electrostatic interactions with environment, and structural stability conformation. It is therefore important obtain a good understanding mutations that affect total charge which arisen across SARS-CoV-2 lineages during course virus' evolution. Results: We analyse change in number ionizable acids corresponding proteins almost 2200 emerged over span pandemic. Our results show previously observed trend toward an increase positive variants concern has essentially stopped emergence early omicron variants. Furthermore, recently greater diversity terms their composition acids. also demonstrate patterns are characteristic related within broader clade division phylogenetic tree. Due ubiquity biological our findings relevant for broad range studies dealing environment. Availability: The data underlying article available online Supplementary Material.

Language: Английский

Changes in total charge on spike protein of SARS-CoV-2 in emerging lineages DOI Creative Commons
Anže Božič, Rudolf Podgornik

Bioinformatics Advances, Journal Year: 2024, Volume and Issue: 4(1)

Published: Jan. 1, 2024

Abstract Motivation Charged amino acid residues on the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been shown to influence its binding different cell surface receptors, non-specific electrostatic interactions with environment, and structural stability conformation. It is therefore important obtain a good understanding mutations that affect total charge which arisen across SARS-CoV-2 lineages during course virus’ evolution. Results We analyse change in number ionizable acids corresponding proteins almost 2200 emerged over span pandemic. Our results show previously observed trend toward an increase positive variants concern has essentially stopped emergence early omicron variants. Furthermore, recently greater diversity terms their composition acids. also demonstrate patterns are characteristic related within broader clade division phylogenetic tree. Due ubiquity biological our findings relevant for broad range studies dealing environment. Availability implementation The data underlying article available Supplementary material.

Language: Английский

Citations

8
Large‐Scale FMO‐MP2 Calculations of the Spike Protein Droplet Model DOI Creative Commons
Hideo Doi, Tatsuya Nakano,

Kota Sakakura

et al.

Journal of Computational Chemistry, Journal Year: 2025, Volume and Issue: 46(4)

Published: Feb. 2, 2025

ABSTRACT The spike protein of SARS‐CoV‐2 is a challenging target for theoretical approaches. Here we report benchmark calculation the droplet model by fragment molecular orbital (FMO) at second‐order Møller‐Plesset perturbation (MP2) level on supercomputer Fugaku. One hundred structure samples from dynamics (MD) simulations were used both closed and open forms this (PDB IDs 6XLU 6XM0 respectively). number total fragments about 20,000, job time per was 2 h 8 racks

Language: Английский

Citations

0
Increased preference for lysine over arginine in spike proteins of SARS-CoV-2 BA.2.86 variant and its daughter lineages DOI Creative Commons
Anže Božič, Rudolf Podgornik

PLoS ONE, Journal Year: 2025, Volume and Issue: 20(4), P. e0320891 - e0320891

Published: April 7, 2025

The COVID-19 pandemic offered an unprecedented glimpse into the evolution of its causative virus, SARS-CoV-2. It has been estimated that since outbreak in late 2019, virus explored all possible alternatives terms missense mutations for sites polypeptide chain. Spike protein exhibits largest sequence variation particular, with many individual impacting target recognition, cellular entry, and endosomal escape virus. Moreover, recent studies unveiled a significant increase total charge on spike during initial period pandemic. While this trend recently come to halt, we perform sequence-based analysis 2665 SARS-CoV-2 variants which shows ionizable amino acids continue occur newly emerging variants, notable differences between lineages from different clades. What is more, show within can acquire positive charge, prominent preference lysine residues over arginine residues. This lysine-to-arginine ratio increased at several points evolution, most BA.2.86 sublineages, including dominant JN.1, KP.3, XEC variants. consequence structural regions now among highest viral species Coronaviridae family. impact high proteins daughter fitness remains unclear; discuss potential mechanisms could play role serve as starting point further studies.

Language: Английский

Citations

0
Genomics-based approach for detection and characterization of SARS-CoV-2 co-infections and diverse viral populations DOI Creative Commons
Bryan Jimenez-Araya,

Aurélie Gourgeon,

Mélissa N’Debi

et al.

Microbiology Spectrum, Journal Year: 2025, Volume and Issue: unknown

Published: May 1, 2025

Due to the continuous genetic diversification of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) over time, co-circulation two different lineages in same region may lead co-infections within a host, situation known contribute emergence hybrid viral populations through genomic recombination. The aim this study was use genomics-based approach identify distinct SARS-CoV-2 patients with disease 2019 (COVID-19), as an indicator potential and recombination events. cohort included 41,224 serial nasopharyngeal swabs positive for RNA, prospectively collected between January 2021 April 2022 part French national surveillance program. Full-length genomes were sequenced by next-generation sequencing (COVIDseq). Intra-host single nucleotide variants (iSNVs) identified, synthetic generated establish thresholds co-infection detection. Eight hundred sixty-one samples iSNV ratios above threshold considered "potential co-infections." Peaks prevalence occurred during periods variants. Co-infection Variants Concern (VoC) confirmed 103 cases, including Alpha-Beta 12 Alpha-Delta 15 Gamma-Delta 4 Delta-Omicron 35 Omicron BA.1-BA.2 37 cases. In conclusion, our suggests higher variant/subvariant events than that previously reported using conventional approaches, particularly characterized multiple lineages, creating increased risk Our results support premise importance approaches detect virus-infected populations, closely related lineages. We implement innovative monitor diversity human population, circulation VOCs. This focused on detecting highly diverse which are facilitate can potentially new recombinant novel characteristics. Monitoring characterizing cases outbreak is key strategy better understanding evolution, especially epidemic periods. However, challenging, their often underestimated. study, we developed be implemented programs applied large datasets. Concern.

Language: Английский

Citations

0
Electrostatic Interaction between SARS-CoV-2 and Charged Surfaces: Spike Protein Evolution Changed the Game DOI
Marc Domingo, Horacio V. Guzman, Matej Kanduč

et al.

Journal of Chemical Information and Modeling, Journal Year: 2024, Volume and Issue: 65(1), P. 240 - 251

Published: Dec. 26, 2024

Previous works show the key role of electrostatics in SARS-CoV-2 virus aspects such as virus-cell interactions or inactivation by ionic surfactants. Electrostatic depend strongly on variant since charge Spike protein (responsible for virus-environment interactions) evolved across variants from highly negative Wild Type (WT) to positive Omicron variant. The distribution also diffuse localized. These facts suggest that should interact with charged surfaces a way changed during evolution. This question is studied here computing electrostatic interaction between WT, Delta and proteins using new method (based Debye-Hückel theory) provides efficiently general results function surface density σ. We found WT spikes dominated repulsive image forces proportional σ2 originating at protein/water interface. On contrary, shows distinct behavior, being attracted negatively repelled positively ones. Therefore, has adsorbing

Language: Английский

Citations

2
An evolutionary theory on virus mutation in COVID-19 DOI Creative Commons
Liaofu Luo, Jun Lv

Virus Research, Journal Year: 2024, Volume and Issue: 344, P. 199358 - 199358

Published: March 22, 2024

With the rapid evolution of SARS-CoV-2, emergence new strains is an intriguing question. This paper presents evolutionary theory to analyze mutations virus and identify conditions that lead generation strains. We represent variants using a 4-letter sequence based on amino acid spike protein employ n-distance algorithm derive variant phylogenetic tree. show theoretically-derived tree aligns with experimental data evolution. Additionally, we propose A-X model, utilizing set existing mutation sites (A) randomly generated (X), calculate Our findings demonstrate sufficient number random iterations can predict macro-lineages when in X large enough. These results provide crucial theoretical basis for understanding SARS-CoV-2.

Language: Английский

Citations

1
Adsorption-Driven Deformation and Footprints of the RBD Proteins in SARS-CoV-2 Variants on Biological and Inanimate Surfaces DOI Creative Commons
Antonio M. Bosch, Horacio V. Guzman, Rúben Pérez

et al.

Journal of Chemical Information and Modeling, Journal Year: 2024, Volume and Issue: 64(15), P. 5977 - 5990

Published: July 31, 2024

Respiratory viruses, carried through airborne microdroplets, frequently adhere to surfaces, including plastics and metals. However, our understanding of the interactions between viruses materials remains limited, particularly in scenarios involving polarizable surfaces. Here, we investigate role receptor-binding domain (RBD) spike protein mutations on adsorption SARS-CoV-2 hydrophobic hydrophilic surfaces employing molecular simulations. To contextualize findings, contrast inanimate with those native biological interfaces, specifically angiotensin-converting enzyme 2. Notably, identify a 2-fold increase structural deformations for protein's receptor binding motif (RBM) onto indicative enhanced shock-absorbing mechanisms. Furthermore, distribution adsorbed amino acids (landing footprints) surface reveals distinct regional asymmetry relative interface, roughly half arranged opposite sites. In spite H-bonds formed at substrate, simulations consistently show higher number contacts interfacial area surface, where wild-type RBD adsorbs more strongly than Delta or Omicron RBDs. contrast, was characterized by distinctive hopping-pattern. The novel mechanisms identified virus embedded high-deformation capacity without losing its secondary structure, which could lead current experimental strategies design virucidal

Language: Английский

Citations

1
An Evolutionary Theory on Virus Mutation in COVID-19 DOI Open Access
Liaofu Luo, Jun Lv

Published: Dec. 26, 2023

With the rapid evolution of SARS-CoV-2, emergence new strains is an intriguing question. This paper presents evolutionary theory to analyze mutations virus and identify conditions that lead generation strains. We represent variants using a 4-letter sequence based on amino acid spike protein employ n-distance algorithm derive variant phylogenetic tree. show theoretically-derived tree aligns with experimental data evolution. Additionally, we propose A-X model, utilizing set existing mutation sites (A) randomly generated (X), calculate Our findings demonstrate sufficient number random iterations can predict macro-lineages when in X large enough. These results provide crucial theoretical basis for understanding SARS-CoV-2.

Language: Английский

Citations

1
Adsorption-driven deformation and landing-footprints of the RBD proteins in SARS-CoV-2 variants onto biological and inanimate surfaces DOI Creative Commons
Antonio M. Bosch, Horacio V. Guzman, Ruben Pérez

et al.

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

Published: Jan. 16, 2024

Abstract Respiratory viruses, carried through airborne microdroplets, frequently adhere to surfaces, including plastics and metals. However, our understanding of the interactions between viruses materials remains limited, particularly in scenarios involving polarizable surfaces. Here, we investigate role receptor-binding domain (RBD) mutations on adsorption SARS-CoV-2 hydrophobic hydrophilic surfaces employing molecular simulations. To contextualize findings, contrast inanimate with those native-biological interfaces, specifically ACE2 receptor. Notably, identify a twofold increase structural deformations for protein’s receptor binding motif onto indicative enhanced shock-absorbing mechanisms. Furthermore, distribution amino acids (landing-footprints) surface reveals distinct regional asymmetry relative biological interface. In spite H-bonds formed at substrate, simulations consistently show higher number contacts interfacial area surface, WT RBD adsorbed more strongly than delta or omicron RBDs. contrast, was characterized by distinctive hopping-pattern. The novel mechanisms identified virus could lead current experimental efforts design virucidal

Language: Английский

Citations

0
An Evolutionary Theory on Virus Mutation in COVID-19 DOI Open Access
Liaofu Luo, Jun Lv

Published: March 26, 2024

With the rapid evolution of SARS-CoV-2, emergence new strains is an intriguing question. This paper presents evolutionary theory to analyze mutations virus and identify conditions that lead generation strains. We represent variants using a 4-letter sequence based on amino acid spike protein employ n-distance algorithm derive variant phylogenetic tree. show theoretically-derived tree aligns with experimental data evolution. Additionally, we propose A-X model, utilizing set existing mutation sites (A) randomly generated (X), calculate Our findings demonstrate sufficient number random iterations can predict macro-lineages when in X large enough. These results provide crucial theoretical basis for understanding SARS-CoV-2.

Language: Английский

Citations

0