Assuntos
Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Antivirais/uso terapêutico , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Monofosfato de Adenosina/administração & dosagem , Monofosfato de Adenosina/efeitos adversos , Monofosfato de Adenosina/provisão & distribuição , Monofosfato de Adenosina/uso terapêutico , Adulto , Alanina/administração & dosagem , Alanina/efeitos adversos , Alanina/provisão & distribuição , Alanina/uso terapêutico , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Antivirais/provisão & distribuição , COVID-19 , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/virologia , Esquema de Medicação , Avaliação de Medicamentos , Humanos , Hidroxicloroquina/efeitos adversos , Hidroxicloroquina/uso terapêutico , Infusões Intravenosas , Pandemias , Placebos , Pneumonia Viral/mortalidade , Pneumonia Viral/virologia , Ensaios Clínicos Controlados Aleatórios como Assunto , SARS-CoV-2 , Fatores de Tempo , Resultado do Tratamento , Carga Viral/efeitos dos fármacosRESUMO
Identification of protein-protein interactions (PPIs) that occur in various cellular processes helps to reveal their potential molecular mechanisms, and there is still an urgent need to develop the assays to explore PPIs in living subjects. Here, we reported a near-infrared split luciferase complementation assay (SLCA) with enhanced bioluminescence produced by cleaving a luciferase, Akaluc, for exploring and visualizing PPIs in living cells and live mice. Compared with the previously developed and widely used red SLCA based on split firefly luciferase (Fluc-SLCA), the signal intensities for PPI recognition in living cells and live mice of the Akaluc-SLCA increased by â¼3.79-fold and â¼18.06-fold in the measured condition, respectively. Additionally, the interactions between the nucleocapsid protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and cellular RNA processing proteins were identified, and the drug evaluation assays were also performed in living cells using Akaluc-SLCA. This study provides a new tool in the near-infrared region for the identification of PPIs in living cells and in vivo and new information for the understanding and treatment of SARS-CoV-2.
Assuntos
COVID-19 , Luciferases de Vaga-Lume , Animais , Avaliação de Medicamentos , Luciferases/genética , Luciferases de Vaga-Lume/metabolismo , Camundongos , Proteínas do Nucleocapsídeo , SARS-CoV-2Assuntos
COVID-19 , Betacoronavirus , Surtos de Doenças , Guia , Resultado do Tratamento , Antivirais , Avaliação de Medicamentos , Hidroxicloroquina , Lopinavir , Janus Quinases , IvermectinaAssuntos
COVID-19 , Betacoronavirus , Surtos de Doenças , Guia , Resultado do Tratamento , Antivirais , Avaliação de Medicamentos , Hidroxicloroquina , Lopinavir , Janus Quinases , IvermectinaAssuntos
COVID-19 , Betacoronavirus , Surtos de Doenças , Resultado do Tratamento , Guia , Antivirais , Avaliação de Medicamentos , Hidroxicloroquina , Lopinavir , Janus Quinases , IvermectinaAssuntos
COVID-19 , Betacoronavirus , Surtos de Doenças , Guia , Resultado do Tratamento , Antivirais , Avaliação de Medicamentos , Hidroxicloroquina , Lopinavir , Janus Quinases , IvermectinaAssuntos
COVID-19 , Betacoronavirus , Surtos de Doenças , Guia , Resultado do Tratamento , Antivirais , Avaliação de Medicamentos , Hidroxicloroquina , Lopinavir , Interleucina-6 , Janus Quinases , IvermectinaRESUMO
The coronavirus disease 2019 pandemic, which was caused by the severe acute respiratory syndrome coronavirus 2, has led to an unprecedented effort to generate real-world evidence on the safety and effectiveness of various treatments. A growing number of observational studies in which the effects of certain drugs were evaluated have been conducted, including several in which researchers assessed whether hydroxychloroquine improved outcomes in infected individuals and whether renin-angiotensin-aldosterone system inhibitors have detrimental effects. In the present article, we review and illustrate how immortal time bias and selection bias were present in several of these studies. Understanding these biases and how they can be avoided may prove important for future observational studies assessing the effectiveness and safety of potentially promising drugs during the coronavirus 19 pandemic.
Assuntos
Tratamento Farmacológico da COVID-19 , Estudos de Coortes , Avaliação de Medicamentos/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Viés , Humanos , Projetos de Pesquisa , SARS-CoV-2Assuntos
COVID-19 , Betacoronavirus , Surtos de Doenças , Guia , Resultado do Tratamento , Antivirais , Avaliação de Medicamentos , Interleucina-6RESUMO
Importance: Continuous assessment of the effectiveness and safety of the US Food and Drug Administration-authorized SARS-CoV-2 vaccines is critical to amplify transparency, build public trust, and ultimately improve overall health outcomes. Objective: To evaluate the effectiveness of the Johnson & Johnson Ad26.COV2.S vaccine for preventing SARS-CoV-2 infection. Design, Setting, and Participants: This comparative effectiveness research study used large-scale longitudinal curation of electronic health records from the multistate Mayo Clinic Health System (Minnesota, Arizona, Florida, Wisconsin, and Iowa) to identify vaccinated and unvaccinated adults between February 27 and July 22, 2021. The unvaccinated cohort was matched on a propensity score derived from age, sex, zip code, race, ethnicity, and previous number of SARS-CoV-2 polymerase chain reaction tests. The final study cohort consisted of 8889 patients in the vaccinated group and 88â¯898 unvaccinated matched patients. Exposure: Single dose of the Ad26.COV2.S vaccine. Main Outcomes and Measures: The incidence rate ratio of SARS-CoV-2 infection in the vaccinated vs unvaccinated control cohorts, measured by SARS-CoV-2 polymerase chain reaction testing. Results: The study was composed of 8889 vaccinated patients (4491 men [50.5%]; mean [SD] age, 52.4 [16.9] years) and 88â¯898 unvaccinated patients (44â¯748 men [50.3%]; mean [SD] age, 51.7 [16.7] years). The incidence rate ratio of SARS-CoV-2 infection in the vaccinated vs unvaccinated control cohorts was 0.26 (95% CI, 0.20-0.34) (60 of 8889 vaccinated patients vs 2236 of 88â¯898 unvaccinated individuals), which corresponds to an effectiveness of 73.6% (95% CI, 65.9%-79.9%) and a 3.73-fold reduction in SARS-CoV-2 infections. Conclusions and Relevance: This study's findings are consistent with the clinical trial-reported efficacy of Ad26.COV2.S and the first retrospective analysis, suggesting that the vaccine is effective at reducing SARS-CoV-2 infection, even with the spread of variants such as Alpha or Delta that were not present in the original studies, and reaffirm the urgent need to continue mass vaccination efforts globally.