Predicting COVID-19 disease severity from SARS-CoV-2 spike protein sequence by mixed effects machine learning DOI Creative Commons
Bahrad A. Sokhansanj, Gail Rosen

Computers in Biology and Medicine, Год журнала: 2022, Номер 149, С. 105969 - 105969

Опубликована: Авг. 17, 2022

Epidemiological studies show that COVID-19 variants-of-concern, like Delta and Omicron, pose different risks for severe disease, but they typically lack sequence-level information the virus. Studies which do obtain viral genome sequences are generally limited in time, location, population scope. Retrospective meta-analyses require time-consuming data extraction from heterogeneous formats to publicly available reports. Fortuitously, a subset of GISAID, global SARS-CoV-2 sequence repository, includes "patient status" metadata can indicate whether record is associated with mild or disease. While GISAID lacks on comorbidities relevant severity, such as obesity chronic it does include age sex use additional attributes modeling. With these caveats, previous efforts have demonstrated genotype-patient status models be fit data, particularly when country-of-origin used an feature. But robust biologically meaningful? This paper shows that, fact, temporal geographic biases submitted well evolving pandemic response, reduction disease due vaccination, create complex issues model development interpretation. poses potential solution: efficient mixed effects machine learning using GPBoost, treating country random effect group. Training validation temporally split emerging Omicron variants demonstrates GPBoost more predictive impact spike protein mutations patient outcomes than fixed XGBoost, LightGBM, forests, elastic net logistic regression models.

Язык: Английский

Mutation N856K in spike reduces fusogenicity and infectivity of Omicron BA.1 DOI Creative Commons

Chunyun Sun,

Huiyu Wang, Ji Yang

и другие.

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Фев. 22, 2023

Язык: Английский

Процитировано

15
Temperature-dependent Spike-ACE2 interaction of Omicron subvariants is associated with viral transmission DOI Creative Commons
Mehdi Benlarbi,

Shilei Ding,

Étienne Bélanger

и другие.

mBio, Год журнала: 2024, Номер 15(8)

Опубликована: Июль 2, 2024

The continued evolution of severe acute respiratory syndrome 2 (SARS-CoV-2) requires persistent monitoring its subvariants. Omicron subvariants are responsible for the vast majority SARS-CoV-2 infections worldwide, with XBB and BA.2.86 sublineages representing more than 90% circulating strains as January 2024. To better understand parameters involved in viral transmission, we characterized functional properties Spike glycoproteins from BA.2.75, CH.1.1, DV.7.1, BA.4/5, BQ.1.1, XBB, XBB.1, XBB.1.16, XBB.1.5, FD.1.1, EG.5.1, HK.3, JN.1. We tested their capacity to evade plasma-mediated recognition neutralization, binding angiotensin-converting enzyme (ACE2), susceptibility cold inactivation, processing, well impact temperature on Spike-ACE2 interaction. found that compared early wild-type (D614G) strain, most subvariants' evolved escape neutralization by plasma individuals who received a fifth dose bivalent (BA.1 or BA.4/5) mRNA vaccine improve ACE2 binding, particularly at low temperatures. Moreover, had best affinity all temperatures tested. processing is associated inactivation. Intriguingly, was significantly growth rates humans. Overall, report Spikes newly emerged relatively stable resistant present improved which associated, temperatures, rates.IMPORTANCEThe gave rise wide range variants harboring new mutations glycoproteins. Several factors have been transmission fitness such plasma-neutralization whether additional could be importance variants' characterize several glycoprotein presents an further temperature. interaction strongly rate, such, represent another parameter affecting transmission.

Язык: Английский

Процитировано

5
Risk of Reinfection, Vaccine Protection, and Severity of Infection with the BA.5 Omicron Subvariant: A Danish Nation-Wide Population-Based Study DOI
Christian Holm Hansen, Nikolaj Ulrik Friis, Peter Bager

и другие.

SSRN Electronic Journal, Год журнала: 2022, Номер unknown

Опубликована: Янв. 1, 2022

Background: Estimates of immunity and severity for the SARS-CoV-2 omicron subvariant BA.5 are important to assess public health impact associated with its rapid global spread despite vaccination. We estimated natural vaccine relative BA.2 in Denmark, a country high mRNA vaccination coverage free-of-charge RT-PCR testing.Methods: This was an observational cohort study including residents 18 years or older test between 10 April 20 June, 2022, identified national COVID-19 surveillance system database information since February, 2020, on tests, wholegenome sequencing, vaccinations hospitalisations positive as main diagnosis. calculated effect prior infection odds ratio (OR) among triple-vaccinated individuals (%protection=1-OR). For we also OR triple-vaccination vs none (ie. effectiveness) hospitalisation. ORs were logistic regression models adjusted age, time, sex, region, comorbidities.Findings: Among 4,809 cases 164,369 test-negative individuals, highly protective against (93.6%, 95%CI92.1-94.8; 96 29,832 omicron). 4,913 31,874 cases, not different (OR1.02, 95%CI0.83-1.26). Although overall number due diagnosis low stable during period, proportion infected increased. In crude analysis hospitalisation (OR 1.04 (0.83-1.31) whereas 1.65 (1.16-2.34). The increased strata age calendar period – two covariates largest contribution confounding OR.Interpretation: found protection from similar effectiveness currently BA.2. covariates, risk which needs confirmation continued period.Funding Statement: None.Declaration Interests: None.Ethics Approval performed under authority task Danish infectious disease control institute, allows Statens Serum Institut perform analyses data existing systems. According law, ethical approval individual consent is required anonymized aggregated register-based studies.

Язык: Английский

Процитировано

21
Neutralization sensitivity, fusogenicity, and infectivity of Omicron subvariants DOI Creative Commons
Xuejun Wang,

Lin Yao,

Hong‐Yun Zhang

и другие.

Genome Medicine, Год журнала: 2022, Номер 14(1)

Опубликована: Дек. 29, 2022

Abstract Background The emergence of SARS-CoV-2 Omicron subvariants has raised questions regarding resistance to immunity by natural infection or immunization. We examined the sensitivity Delta and (BA.1, BA.1.1, BA.2, BA.2.12.1, BA.4/5, BA.3) neutralizing antibodies from BBIBP-CorV-vaccinated BBIBP-CorV- ZF2001-boosted individuals, as well individuals with BA.1 breakthrough infections, determined their fusogenicity infectivity. Methods In this cross-sectional study, serum samples two doses 1 ( n = 36), 3 7 37) months after second dose; 25) 30) individuals; fully vaccinated 26) were collected. serum-neutralizing reactivity potency bebtelovimab assessed against D614G, Delta, through a pseudovirus neutralization assay. infectivity cell-cell fusion assay assay, respectively. Results markedly escaped vaccine-elicited BBIBP-CorV comparable efficiency. A third dose vaccination ZF2001 increased antibody titers breadth three subvariants. infections induced D614G variants, whereas elicited stronger broader response than infections. BA.2.12.1 BA.4/5 are more resistant Bebtelovimab had no significant loss Cell culture experiments showed be less fusogenic have higher Conclusions These findings important public health implications highlight importance repeated exposure antigens broaden

Язык: Английский

Процитировано

19
Structural insights into immune escape at killer T cell epitope by SARS-CoV-2 Spike Y453F variants DOI Creative Commons

Shasha Deng,

Zhihao Xu,

Meihua Wang

и другие.

Journal of Biological Chemistry, Год журнала: 2024, Номер 300(8), С. 107563 - 107563

Опубликована: Июль 11, 2024

Язык: Английский

Процитировано

4
SARS-CoV-2 spike protein in infectivity DOI
Alaa Muayad Altaie, Rania Hamdy,

Mohamed I. Husseiny

и другие.

Elsevier eBooks, Год журнала: 2025, Номер unknown, С. 21 - 56

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

0
Exploring Healthcare and Public Health Implications via Temporal Analysis of Human–Virus Interactions Leveraging Adversarial Networks and Saliency Maps DOI Creative Commons

N Srivastava,

Logesh Ravi,

Malathi Devarajan

и другие.

Applied Artificial Intelligence, Год журнала: 2025, Номер 39(1)

Опубликована: Март 14, 2025

Viruses are prone to rapid mutations that enhance traits like transmissibility and resistance treatments. The adaptability complicates the development of effective vaccines. study investigates dynamic interactions between humans COVID-19 virus through time-series analysis, focusing on how these evolve over time. A novel approach was introduced using adversarial networks model relationship human viral entities, capturing their temporal dynamics. Two interdependent models trained within a framework, allowing us forecast identify influential features. Saliency maps were utilized visualize factors affecting technique helps reveal specific properties shift in response factors. findings aim understanding human-virus dynamics, particularly for COVID-19, offering potential insights public health strategies interventions. By combining with saliency visualization, provides an intensive analyzing interpreting complex viruses.

Язык: Английский

Процитировано

0
The Impact of Mutation Sets in Receptor-Binding Domain of SARS-CoV-2 Variants on Stability of the RBD–ACE2 Complex DOI Creative Commons
Mykyta Peka, Viktor Balatsky

Future Virology, Год журнала: 2023, Номер 18(4), С. 225 - 242

Опубликована: Март 1, 2023

Aim: Bioinformatic analysis of mutation sets in receptor-binding domain (RBD) currently and previously circulating SARS-CoV-2 variants concern (VOCs) interest (VOIs) to assess their ability bind the ACE2 receptor. Methods:In silico sequence structure-oriented approaches were used evaluate impact single multiple mutations. Results: Mutations detected VOCs VOIs led reduction binding free energy RBD-ACE2 complex, forming additional chemical bonds with ACE2, an increase complex stability. Conclusion: Mutation characteristic have effects on affinity associated amino acid interactions at sites, as well acquisition other viral adaptive advantages.The infectious potential (Alpha, Beta, Gamma, Delta, Omicron, etc.) that causes COVID-19 is mainly due virus Particularly important for development disease interaction coronavirus spike protein a receptor surface human cell, result which penetrates cell. Angiotensin-binding enzyme (ACE2) such humans, there protein. In this study, using bioinformatic methods, mutations RBD was carried out find influence functionality interact high stability, ultimately leads infection. A number virus. More recent more than one RBD, so are complex. It constantly evolving, increasing receptor, avoiding immune response. The Omicron variant, has least 15 most successful these directions.

Язык: Английский

Процитировано

10
Antibody evasion associated with the RBD significant mutations in several emerging SARS-CoV-2 variants and its subvariants DOI
Manojit Bhattacharya, Srijan Chatterjee, Sang‐Soo Lee

и другие.

Drug Resistance Updates, Год журнала: 2023, Номер 71, С. 101008 - 101008

Опубликована: Сен. 22, 2023

Язык: Английский

Процитировано

10
Impact of mutations defining SARS-CoV-2 Omicron subvariants BA.2.12.1 and BA.4/5 on Spike function and neutralization DOI Creative Commons
Chiara Pastorio, Sabrina Noettger, Rayhane Nchioua

и другие.

iScience, Год журнала: 2023, Номер 26(11), С. 108299 - 108299

Опубликована: Окт. 27, 2023

Additional mutations in the viral Spike protein helped BA.2.12.1 and BA.4/5 SARS-CoV-2 Omicron subvariants to outcompete parental BA.2 subvariant. Here, we determined functional impact of that newly emerged (L452Q, S704L) (Δ69-70, L452R, F486V, R493Q) proteins. Our results show mutation L452Q/R or F486V typically increases R493Q S704L impair Spike-mediated infection. In combination, changes Δ69-70, contribute higher infectiousness fusogenicity Spike. L452R/Q are mainly responsible for reduced sensitivity neutralizing antibodies. However, combined required full infectivity, TMPRSS2 dependency, immune escape Thus, it is specific combination allows increased functionality evasion, which helps explain temporary dominance pathogenicity these subvariants.

Язык: Английский

Процитировано

9