Omicron (B.1.1.529) - A new heavily mutated variant: Mapped location and probable properties of its mutations with an emphasis on S-glycoprotein

International Journal of Biological Macromolecules, Journal Year: 2022, Volume and Issue: 219, P. 980 - 997

Published: Aug. 8, 2022

Language: Английский

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Advances in RT-LAMP for COVID-19 testing and diagnosis

Expert Review of Molecular Diagnostics, Journal Year: 2023, Volume and Issue: 23(1), P. 9 - 28

Published: Jan. 2, 2023

Introduction : The SARS-CoV-2 pandemic, and the subsequent limitations on standard diagnostics, has vastly expanded user base of Reverse Transcription Loop-mediated isothermal Amplification (RT-LAMP) in fundamental research development. RT-LAMP also penetrated commercial markets, with emergency use authorizations for clinical diagnosis.Areas covered This review discusses role within context other technologies like RT-qPCR rapid antigen tests, progress sample preparation strategies to enable simplified workflow directly from specimens, new challenges primer assay design evolving prominent detection modalities including colorimetric CRISPR-mediated methods, translational development applications.Expert opinion occupies a middle ground between tests. simplicity approaches that making it suitable point-of-care use, but sensitivity nears RT-qPCR. still lags understanding mechanism, interplay performance. Industry is now beginning address issues around scalability usability, which could finally LAMP find future widespread application as diagnostic conditions, pathogens pandemic potential.

Language: Английский

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In Silico Discovery of Small Molecule Modulators Targeting the Achilles’ Heel of SARS-CoV-2 Spike Protein

ACS Central Science, Journal Year: 2023, Volume and Issue: 9(2), P. 252 - 265

Published: Feb. 8, 2023

The spike protein of SARS-CoV-2 has been a promising target for developing vaccines and therapeutics due to its crucial role in the viral entry process. Previously reported cryogenic electron microscopy (cryo-EM) structures have revealed that free fatty acids (FFA) bind with protein, stabilizing closed conformation reducing interaction host cell vitro. Inspired by these, we utilized structure-based virtual screening approach against conserved FFA-binding pocket identify small molecule modulators which helped us six hits micromolar binding affinities. Further evaluation their commercially available synthesized analogs enabled discover series compounds better affinities solubilities. Notably, our identified exhibited similar proteins prototypic currently circulating Omicron BA.4 variant. Furthermore, cryo-EM structure compound SPC-14 bound could shift conformational equilibrium toward conformation, is human ACE2 (hACE2) inaccessible. Our targeting serve as starting point future development broad-spectrum COVID-19 intervention treatments.

Language: Английский

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Animal Models, Zoonotic Reservoirs, and Cross-Species Transmission of Emerging Human-Infecting Coronaviruses

Annual Review of Animal Biosciences, Journal Year: 2023, Volume and Issue: 11(1), P. 1 - 31

Published: Feb. 15, 2023

Over the past three decades, coronavirus (CoV) diseases have impacted humans more than any other emerging infectious disease. The recent emergence of severe acute respiratory syndrome 2 (SARS-CoV-2), causative agent COVID-19 (coronavirus disease 2019), has resulted in huge economic disruptions and loss human lives. SARS-CoV-2 genome was found to mutate rapidly due sustained transmission potentially animals, resulting variants concern (VOCs) that threaten global health. However, primary difficulties are filling current knowledge gaps terms origin modalities for these viruses. Because many CoVs threatening health suspected a zoonotic origin, identifying animal hosts implicated spillover or spillback events would be beneficial pandemic management prevent future outbreaks. In this review, wesummarize models, reservoirs, cross-species CoVs. Finally, we comment on potential sources Omicron VOCs new recombinants currently under investigation.

Language: Английский

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Advancing pathogen genomics in resource-limited settings

Cell Genomics, Journal Year: 2023, Volume and Issue: 3(12), P. 100443 - 100443

Published: Nov. 17, 2023

Genomic sequencing has emerged as a powerful tool to enhance early pathogen detection and characterization with implications for public health clinical decision making. Although widely available in developed countries, the application of genomics among low-resource, high-disease burden settings remains at an stage. In these contexts, tailored approaches integrating within infectious disease control programs will be essential optimize cost efficiency impact. We propose framework embedding national surveillance plans across spectrum laboratory capacities. adopt approach examine its high-priority diseases relevant resource-limited settings. For each grouping, we assess value proposition inform decision-making, alongside contribution toward research development novel diagnostics, therapeutics, vaccines.

Language: Английский

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The Potential of Nanobodies for COVID-19 Diagnostics and Therapeutics

Molecular Diagnosis & Therapy, Journal Year: 2023, Volume and Issue: 27(2), P. 193 - 226

Published: Jan. 19, 2023

Language: Английский

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Prevalence of symptoms, comorbidities, and reinfections in individuals infected with Wild-Type SARS-CoV-2, Delta, or Omicron variants: a comparative study in western Mexico

Frontiers in Public Health, Journal Year: 2023, Volume and Issue: 11

Published: April 27, 2023

Introduction The variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been classified into interest (VOIs) or concern (VOCs) to prioritize global monitoring and research on with potential risks public health. SARS-CoV-2 high-rate mutation can directly impact the clinical disease progression, epidemiological behavior, immune evasion, vaccine efficacy, transmission rates. Therefore, surveillance is crucial for controlling COVID-19 pandemic. In present study, we aimed describe prevalence wild-type (WT) Delta Omicron in Jalisco State, Mexico, from 2021 2022, evaluate possible association these manifestations COVID-19. Methods Four thousand ninety-eight patients diagnosed by real-time PCR (COVIFLU, Genes2Life, Mexico) nasopharyngeal samples January 2022 were included. Variant identification was performed RT-qPCR Master Mut Kit (Genes2Life, Mexico). A study population follow-up identify who had experienced reinfection after being vaccinated. Results Discussion Samples grouped according identified mutations: 46.3% Omicron, 27.9% Delta, 25.8% WT. proportions dry cough, fatigue, headache, muscle pain, conjunctivitis, fast breathing, diarrhea, anosmia, dysgeusia significantly different among abovementioned groups ( p < 0.001). Anosmia mainly found WT-infected patients, while rhinorrhea sore throat more prevalent infected variant. For follow-up, 836 answered, which 85 cases (9.6%); VOC that caused all reported cases. this demonstrate variant biggest outbreak during pandemic late December mid-February but a less form than one demonstrated co-analysis mutations outcomes health strategy infer could increase severity even be an indicator long-term sequelae

Language: Английский

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Host Response of Syrian Hamster to SARS-CoV-2 Infection including Differences with Humans and between Sexes

Viruses, Journal Year: 2023, Volume and Issue: 15(2), P. 428 - 428

Published: Feb. 3, 2023

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has highlighted the importance having proper tools and models to study pathophysiology emerging infectious diseases test therapeutic protocols, assess changes in viral phenotypes, evaluate effects evolution. This provided a comprehensive characterization Syrian hamster (Mesocricetus auratus) as an animal model for SARS-CoV-2 infection using different approaches (description clinical signs, load, receptor profiling, host immune response) targeting four organs (lungs, intestine, brain, PBMCs). Our data showed that both male female hamsters were susceptible developed disease similar one observed patients with COVID-19 included moderate pulmonary lesions, inflammation, recruitment system lungs at systemic level. However, all animals recovered within 14 days without developing pathology seen humans, none them died. We found faint evidence intestinal neurological tropism associated absence lesions minimal response intestines brains, which another crucial difference multiorgan impairment COVID-19. When comparing hamsters, we males sustained higher RNA shedding replication lungs, suffered from more symptoms histopathological triggered inflammation. Overall, these confirmed suitable mild reflected sex-related differences against virus humans.

Language: Английский

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Analysis of SARS-CoV-2 genome evolutionary patterns

Microbiology Spectrum, Journal Year: 2024, Volume and Issue: 12(2)

Published: Jan. 10, 2024

ABSTRACT The spread of SARS-CoV-2 virus accompanied by public availability abundant sequence data provides a window for the determination viral evolutionary patterns. In this study, genome sequences were collected from seven countries in period January 2020–December 2022. classified into three phases, namely, pre-vaccination, post-vaccination, and recent period. Comparison was performed between these phases based on parameters like mutation rates, selection pressure (d N /d S ratio), transition to transversion ratios (T i /T v ). Similar comparisons among variants. Statistical significance tested using Graphpad unpaired t -test. analysis showed an increase percent genomic rates post-vaccination periods across all pre-vaccination sequences. Mutation highest NSP3, S, N, NSP12b before increased further after vaccination. NSP4 largest change d purifying that shifted toward neutral ORF8, ORF3a, ORF10 under positive Shift driven E, ORF7a vaccination set. sequences, observed NSP1, NSP13. T decreased with time. C→U G→U most frequent transitions transversions. However, U→G Omicron variant had while Delta ratio. Protein-wise ratio also seen vary different IMPORTANCE To best our knowledge, there exists no other large-scale study protein-wise patterns during time course evolution countries. Analyzing view varying spatial, temporal, biological signals is important diagnostics, therapeutics, pharmacovigilance SARS-CoV-2.

Language: Английский

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Cross-Reactivity of SARS-CoV-2 Nucleocapsid-Binding Antibodies and Its Implication for COVID-19 Serology Tests

Viruses, Journal Year: 2022, Volume and Issue: 14(9), P. 2041 - 2041

Published: Sept. 14, 2022

The emergence of the new coronavirus SARS-CoV-2 in late 2019 led to global pandemic COVID-19, causing a profound socioeconomic crisis. Adequate diagnostic tools need be developed control ongoing spread infection. Virus-specific humoral immunity COVID-19 patients and those vaccinated with specific vaccines has been characterized numerous studies, mainly using Spike protein-based serology tests. However, protein specifically its receptor-binding domain (RBD) are mutation-prone, suggesting reduced sensitivity validated tests detecting antibodies raised variants concern (VOC). viral nucleocapsid (N) is more conserved compared Spike, but little known about cross-reactivity N-specific between ancestral B.1 virus different VOCs. Here, we generated recombinant N phosphoproteins from strains analyzed magnitude convalescent sera an in-house N-based ELISA test system. We found strong positive correlation anti-N (B.1) various VOCs COVID-19-recovered patients, that N-binding highly cross-reactive, most immunogenic epitopes within this not under selective pressure. Overall, our study suggests RBD-based should timely updated reflect constantly evolving nature protein, whereas systems can used for analysis regardless strain caused

Language: Английский

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