Genome‐based comparison between the recombinant SARS‐CoV‐2 XBB and its parental lineages

Journal of Medical Virology, Год журнала: 2023, Номер 95(3)

Опубликована: Фев. 28, 2023

Abstract Recombination is the main contributor to RNA virus evolution, and SARS‐CoV‐2 during pandemic produced several recombinants. The most recent recombinant lineage labeled XBB, also known as Gryphon, which arose from BJ.1 BM.1.1.1. Here we performed a genome‐based survey aimed compare new with its parental lineages that never became dominant. Genetic analyses indicated XBB first descendant XBB.1 show an evolutionary condition typical of blind background no further epidemiologically relevant descendant. variability expansion capabilities are slightly higher than lineages. Bayesian Skyline Plot indicates reached plateau around October 6, 2022 after initial rapid growth viral population size did not expand, November 10, levels genetic decreased. Simultaneously reduction size, increase sub‐lineage occurred, in turn 9, showing kind vicariance direct progenitors. Structure analysis affinity for ACE2 surface XBB/XBB.1 RBDs weaker BA.2 RBD. In conclusion, at present do evidence about particular danger or high capability. Genome‐based monitoring must continue uninterrupted individuate if mutations can make more dangerous generate subvariants different

Язык: Английский

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Evolving Real-World Effectiveness of Monoclonal Antibodies for Treatment of COVID-19

Annals of Internal Medicine, Год журнала: 2023, Номер 176(4), С. 496 - 504

Опубликована: Апрель 1, 2023

Background: Treatment guidelines and U.S. Food Drug Administration emergency use authorizations (EUAs) of monoclonal antibodies (mAbs) for treatment high-risk outpatients with mild to moderate COVID-19 changed frequently as different SARS-CoV-2 variants emerged. Objective: To evaluate whether early outpatient mAbs, overall by mAb product, presumed variant, immunocompromised status, is associated reduced risk hospitalization or death at 28 days. Design: Hypothetical pragmatic randomized trial from observational data comparing mAb-treated patients a propensity score–matched, nontreated control group. Setting: Large health care system. Participants: High-risk eligible under any EUA positive test result 8 December 2020 31 August 2022. Intervention: Single-dose intravenous bamlanivimab, bamlanivimab–etesevimab, sotrovimab, bebtelovimab, subcutaneous casirivimab–imdevimab administered within 2 days result. Measurements: The primary outcome was among treated versus group (no ≥3 after date). Results: 4.6% in 2571 7.6% 5135 (risk ratio [RR], 0.61 [95% CI, 0.50 0.74]). In sensitivity analyses, the corresponding RRs 1- 3-day grace periods were 0.59 0.49, respectively. subgroup those receiving mAbs when Alpha Delta be predominant had estimated 0.55 0.53, respectively, compared 0.71 Omicron variant period. Relative estimates individual products all suggested lower death. Among patients, RR 0.45 (CI, 0.28 0.71). Limitations: Observational study design, date rather than genotyping, no on symptom severity, partial vaccination status. Conclusion: Early various variants. Primary Funding Source: None.

Язык: Английский

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Cationic crosslinked carbon dots-adjuvanted intranasal vaccine induces protective immunity against Omicron-included SARS-CoV-2 variants

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Май 9, 2023

Abstract Mucosal immunity plays a significant role in the first-line defense against viruses transmitted and infected through respiratory system, such as SARS-CoV-2. However, lack of effective safe adjuvants currently limits development COVID-19 mucosal vaccines. In current study, we prepare an intranasal vaccine containing cationic crosslinked carbon dots (CCD) SARS-CoV-2 antigen, RBD-HR with spontaneous antigen particlization. Intranasal immunization CCD/RBD-HR induces high levels antibodies broad-spectrum neutralization authentic viruses/pseudoviruses Omicron-included variants protects immunized female BALB/c mice from Omicron infection. Despite strong systemic cellular immune response stimulation, also potent determined by generation tissue-resident T cells lungs airway. Moreover, not only activates professional antigen-presenting (APCs), dendritic cells, but effectively targets nasal epithelial promotes binding via sialic acid, surprisingly provokes cells. We demonstrate that CCD is promising adjuvant for provoking might be candidate many types infectious diseases, including COVID-19.

Язык: Английский

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An update on the anti-spike monoclonal antibody pipeline for SARS-CoV-2

Clinical Microbiology and Infection, Год журнала: 2024, Номер 30(8), С. 999 - 1006

Опубликована: Апрель 24, 2024

Язык: Английский

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Discovery of novel papain-like protease inhibitors for potential treatment of COVID-19

European Journal of Medicinal Chemistry, Год журнала: 2023, Номер 254, С. 115380 - 115380

Опубликована: Апрель 17, 2023

Язык: Английский

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Comparative Review of the State of the Art in Research on the Porcine Epidemic Diarrhea Virus and SARS-CoV-2, Scope of Knowledge between Coronaviruses

Viruses, Год журнала: 2024, Номер 16(2), С. 238 - 238

Опубликована: Фев. 2, 2024

This review presents comparative information corresponding to the progress in knowledge of some aspects infection by porcine epidemic diarrhea virus (PEDV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) coronaviruses. PEDV is an alphacoronavirus great economic importance due million-dollar losses it generates pig industry. has many similarities SARS-CoV-2 betacoronavirus that causes COVID-19 disease. possible scenarios for based on collected literature tools or strategies currently developed would be useful research. The speed study generation control pandemic was derived from infections caused other human coronaviruses such as (SARS) middle east (MERS). Therefore, obtained several coronaviruses, current future behavior could inferred and, with large amount COVID-19, improved probably new emerging re-emerging

Язык: Английский

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SARS-CoV-2 Omicron: Viral Evolution, Immune Evasion, and Alternative Durable Therapeutic Strategies

Viruses, Год журнала: 2024, Номер 16(5), С. 697 - 697

Опубликована: Апрель 28, 2024

Since the SARS-CoV-2 Omicron virus has gained dominance worldwide, its continual evolution with unpredictable mutations and patterns revoked all authorized immunotherapeutics. Rapid viral also necessitated several rounds of vaccine updates in order to provide adequate immune protection. It remains imperative understand how evolves into different subvariants causes escape as this could help reevaluate current intervention strategies mostly implemented clinics emergency measures counter pandemic and, importantly, develop new solutions. Here, we a review focusing on major events evolution, including features spike mutation that lead evasion against monoclonal antibody (mAb) therapy vaccination, suggest alternative durable options such ACE2-based experimental therapies superior mAbs address unprecedented virus. In addition, type unique virus-trapping molecules can zoonotic SARS coronaviruses, either from unknown animal hosts or established wild-life reservoirs SARS-CoV-2, even seasonal alpha coronavirus NL63 depends human ACE2 for infection.

Язык: Английский

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Subsequent Waves of Convergent Evolution in SARS-CoV-2 Genes and Proteins

Vaccines, Год журнала: 2024, Номер 12(8), С. 887 - 887

Опубликована: Авг. 5, 2024

Beginning in 2022, following widespread infection and vaccination among the global population, SARS-CoV-2 virus mainly evolved to evade immunity derived from vaccines past infections. This review covers convergent evolution of structural, nonstructural, accessory proteins SARS-CoV-2, with a specific look at common mutations found long-lasting infections that hint potentially reverting an enteric sarbecovirus type.

Язык: Английский

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Antibody drugs targeting SARS-CoV-2: Time for a rethink?

Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 176, С. 116900 - 116900

Опубликована: Июнь 10, 2024

Язык: Английский

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Digital modeling by biomedical informatics analysis predicts suppression of COVID-19 infectivity via ‘targeting oligonucleotide-directed devolution’

Опубликована: Март 20, 2025

Aim: Genetic instability represents the hallmark of carcinogenesis. For cancer, retinoblastoma (RB) gene defect allowing genetic was successfully exploited to eliminate cancer. Similarly, this study aims assess severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein’s S1/S2 furin cleavage site in hopes applying oligonucleotide-based therapeutics suppress infectivity by exploiting hypermutability. Methods: The Basic Local Alignment Search Tool used search for homology. Protein or nucleotide sequences were obtained from National Center Biotechnology Information database. BioEdit multiple sequence alignment. Python-enhanced molecular graphics program modeling. Results: To feasibility, comparative alignment performed on plus juxtaposing residues SARS-CoV-2 and avian infectious bronchitis virus (IBV) isolate AL/7052/97 that belongs distinct genus. IBV amino acids correlating 678-TNSPRRARSVASQS protein deciphered (nine identical, two conserved, displaced, one unconserved). encoding nucleotides exhibited 14 identities, three transitions (C>U U>C, two; G>A A>G, one), 15 transversions (U>A A>U, eight; C>G G>C, six; G>U U>G, one) with mostly complementary base (14/15) transversion. Analysis variants corroborates continues evolve. overall data portrays an evolutionarily dynamic nature site. potential role intragenomic ‘microhomology-mediated template switching’ RNA-dependent RNA polymerase is described. Conclusions: apply virolytic pressure, peptide-guided oligonucleotides targeting site-encoding may be deployed trigger genomic degradation. A consequence resistant (if emerge) carry mutation(s) abrogate hybridization, which (by default) encode defective substrate furin. Thus, through ‘targeting directed devolution’ site, attenuated. An alternative strategy therapeutic editing adenosine deaminases acting (ADAR) mentioned.

Язык: Английский

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