Molnupiravir increases SARS‐CoV‐2 genome diversity and complexity: A case‐control cohort study

Journal of Medical Virology, Journal Year: 2024, Volume and Issue: 96(5)

Published: May 1, 2024

Abstract Molnupiravir, an oral direct‐acting antiviral effective in vitro against SARS‐CoV‐2, has been largely employed during the COVID‐19 pandemic, since December 2021. After marketing and widespread usage, a progressive increase SARS‐CoV‐2 lineages characterized by higher transition/transversion ratio, characteristic signature of molnupiravir action, appeared Global Initiative on Sharing All Influenza Data (GISAID) International Nucleotide Sequence Database Collaboration (INSDC) databases. Here, we assessed drug effects whole‐genome sequencing 38 molnupiravir‐treated persistently positive outpatients tested before after treatment. Seventeen tixagevimab/cilgavimab‐treated served as controls. Mutational analyses confirmed that exhibits increased ratio seven days initiation molnupiravir. Moreover observed G‐>A compared to controls, which was not related apolipoprotein B mRNAediting enzyme, catalytic polypeptide‐like (APOBEC) activity. In addition, demonstrated for first time diversity complexity viral quasispecies.

Language: Английский

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Impact of Treatment with Anti-CD20 Monoclonal Antibody on the Production of Neutralizing Antibody Against Anti–SARS-CoV-2 Vaccination in Mature B-Cell Neoplasms

Infection and Drug Resistance, Journal Year: 2023, Volume and Issue: Volume 16, P. 509 - 519

Published: Jan. 1, 2023

Background and Purpose: Anti-CD20 monoclonal antibodies (MoAbs), rituximab (RIT), obinutuzumab (OBZ) are the central components of immunochemotherapy for B-cell lymphoma (BCL). However, these agents potentially cause depletion, resulting in impairment antibody (Ab) production. During severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, optimal prediction Ab response against anti–SARS-CoV-2 vaccination is critically important patients with BCL treated by depletion therapeutics to prevent disease 2019 (COVID-19). Patients Methods: We investigated effect using RIT and/or OBZ on 131 various types who received second SARS-CoV-2 mRNA vaccine either after, during, or before containing B-cell–depleting moiety between June November 2021 at seven institutes belonging Kyoto Clinical Hematology Study Group. The SARS-Cov-2 neutralizing (nAb) was measured from 14 207 days after dose iFlash3000 automatic analyzer iFlash-2019-nCoV Nab kit. Results: Among 86 within 12 months therapy, 8 (9.3%) were seropositive. In 30 22 (73%) 15 subjected therapy vaccination, (13%) multivariate analysis indicated that an interval subsequent significantly associated effective Receiver operating characteristic curve identified threshold period anti-CD20 MoAb treatment, which determines seropositivity SARS-CoV-2, be 342 days. Conclusion: use a critical risk poor BCL. Keywords: COVID-19, vaccine, lymphoma,

Language: Английский

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A Clinical Update on SARS-CoV-2: Pathology and Development of Potential Inhibitors

Current Issues in Molecular Biology, Journal Year: 2023, Volume and Issue: 45(1), P. 400 - 433

Published: Jan. 4, 2023

SARS-CoV-2 (severe acute respiratory syndrome) is highly infectious and causes severe distress syndrome (SARD), immune suppression, multi-organ failure. For SARS-CoV-2, only supportive treatment options are available, such as oxygen therapy, ventilator support, antibiotics for secondary infections, mineral fluid treatment, a significant subset of repurposed effective drugs. Viral targeted inhibitors the most suitable molecules, ACE2 (angiotensin-converting enzyme-2) RBD (receptor-binding domain) protein-based inhibitors, host proteases, viral proteases 3CLpro (3C-like proteinase) PLpro (papain-like protease), replicative enzymes, attachment to receptor TMPRSS2 (transmembrane serine proteinase 2), HR1 (Heptad Repeat 1)–HR2 2) interaction at S2 protein coronavirus, etc. Targeting cathepsin L proteinase, peptide analogues, monoclonal antibodies, chimaeras interferes with spike protein’s ability fuse membrane. Even tremendous progress made, creating drugs remains difficult. To develop COVID-19 alternatives, clinical studies examining variety therapy categories, including antivirals, cell-based diagnostic medicines, more. In this article, we discuss recent updates on infection, characteristics, diagnosis, immunopathology, new emergence variant, various approaches drug development options. The therapies has been complicated by global occurrence many mutations. Discussion manuscript will provide insight into pathophysiology development.

Language: Английский

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Pre-exposure Prophylaxis with Tixagevimab-cilgavimab did not Reduce Severity of COVID-19 in Lung Transplant Recipients with Breakthrough Infection

Transplantation Direct, Journal Year: 2023, Volume and Issue: 9(6), P. e1485 - e1485

Published: May 12, 2023

Lung transplant recipients (LTRs) have an increased risk of COVID-19-related morbidity and mortality. Tixagevimab-cilgavimab (tix-cil) is a long-acting monoclonal antibody combination granted Emergency Use Authorization approval by the US Food Drug Administration for COVID-19 pre-exposure prophylaxis (PrEP) in immunocompromised patients. We sought to determine whether tix-cil 300-300 mg reduced incidence disease severity severe acute respiratory syndrome coronavirus 2 infection LTRs during Omicron wave.We performed retrospective, single-center cohort study who had received diagnosis between December 2021 August 2022. compared baseline characteristics clinical outcomes after PrEP those did not. then conducted propensity-score matching based on therapeutic interventions groups.Of 203 343 not, 24 (11.8%) 57 (16.6%), respectively, developed symptomatic (hazard ratio [HR], 0.669; 95% confidence interval [CI], 0.415-1.079; P = 0.099). The hospitalization rate with wave trended lower group than non-tix-cil (20.8% versus 43.1%; HR, 0.430; CI, 0.165-1.118; 0.083). In propensity-matched analyses, 17 not similar rates (HR, 0.468; 0.156-1.402; 0.175), intensive care unit admission 3.096; 0.322-29.771; 0.328), mechanical ventilation 1.958; 0.177-21.596; 0.583), survival 1.015; 0.143-7.209; 0.988). mortality was high both propensity-score-matched groups (11.8%).Breakthrough common among despite PrEP, possibly due efficacy antibodies against variant. Tix-cil may reduce LTRs, but it wave.

Language: Английский

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Pre‐exposure prophylaxis with tixagevimab/cilgavimab in patients with chronic lymphocytic leukaemia treated with targeted agents

British Journal of Haematology, Journal Year: 2023, Volume and Issue: 201(3), P. 564 - 567

Published: Feb. 22, 2023

Language: Английский

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