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1.
Luminescence ; 39(6): e4792, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38845344

RESUMO

Favipiravir (FVP) is an oral antiviral drug approved in 2021 for the treatment of COVID-19. It is a pyrazine derivative that can be integrated into anti-viral RNA products to inhibit viral replication. While, adenine is a purine nucleobase that is found in deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) to generate genetic information. For the first time, the binding mechanism between FVP and adenine was determined using different techniques, including UV-visible spectrophotometry, spectrofluorimetry, synchronous fluorescence (SF) spectroscopy, Fourier transform infrared (FTIR), fluorescence resonance energy transfer (FRET), and metal ion complexation. The fluorescence spectra indicated that FVP is bound to adenine via Van der Waals forces and hydrogen bonding through a spontaneous binding process (ΔGο < 0). The quenching mechanism was found to be static. Various temperature settings were used to investigate thermodynamic characteristics, such as binding forces, binding constants, and the number of binding sites. The reaction parameters, including the enthalpy change (ΔHο) and entropy change (ΔSο), were calculated using Van't Hoff's equation. The findings demonstrated that the adenine-FVP binding was endothermic. Furthermore, the results of the experiments revealed that some metal ions (K+, Ca+2, Co+2, Cu+2, and Al+3) might facilitate the binding interaction between FVP and adenine. Slight changes are observed in the FTIR spectra of adenine, indicating the binding interaction between adenine and FVP. This study may be useful in understanding the pharmacokinetic characteristics of FVP and how the drug binds to adenine to prevent any side effects.


Assuntos
Nucleotídeos de Adenina , Amidas , Antivirais , Pirazinas , Termodinâmica , Pirazinas/química , Pirazinas/metabolismo , Amidas/química , Amidas/metabolismo , Nucleotídeos de Adenina/química , Nucleotídeos de Adenina/metabolismo , Antivirais/química , Antivirais/farmacologia , Antivirais/metabolismo , Espectroscopia de Infravermelho com Transformada de Fourier , Espectrometria de Fluorescência , Transferência Ressonante de Energia de Fluorescência , Espectrofotometria Ultravioleta , Sítios de Ligação , Adenina/química , Adenina/metabolismo
2.
BMC Infect Dis ; 24(1): 564, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38844861

RESUMO

This single-centre retrospective cohort study reports on the results of a descriptive (non-comparative) retrospective cohort study of early initiation of antivirals and combined monoclonal antibody therapy (mAbs) in 48 severely immunocompromised patients with COVID-19. The study assessed the outcomes and the duration of viral shedding. The patients started early combined therapy (ECT) a median of 2 days (interquartile range [IQR]: 1-3 days) after the diagnosis of SARS-CoV-2 infection. Except for 1 patient who died due COVID-19-related respiratory failure, patients had their first negative nasopharyngeal swab result after a median of 11 days (IQR: 6-17 days) after starting combined therapy. There were no reports of severe side effects. During a follow-up period of 512 days (interquartile range [IQR]: 413-575 days), 6 patients (12.5%) died and 16 (33.3%) were admitted to hospital. Moreover, 12 patients (25%) were diagnosed with SARS-CoV-2 reinfection a median of 245 days (IQR: 138-401 days) after starting combined treatment. No relapses were reported. Although there was no comparison group, these results compare favourably with the outcomes of severely immunocompromised patients with COVID-19 reported in the literature.


Assuntos
Antivirais , Tratamento Farmacológico da COVID-19 , COVID-19 , Hospedeiro Imunocomprometido , SARS-CoV-2 , Humanos , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , COVID-19/imunologia , COVID-19/mortalidade , Antivirais/uso terapêutico , Antivirais/administração & dosagem , SARS-CoV-2/imunologia , Idoso , Eliminação de Partículas Virais/efeitos dos fármacos , Quimioterapia Combinada , Adulto , Resultado do Tratamento , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais/administração & dosagem
3.
J Med Case Rep ; 18(1): 271, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38845030

RESUMO

OBJECTIVE: Extravasation of infused drugs is not a rare problem in medical practice. Acyclovir is a vesicant and an antiviral medication commonly used for young children. In the present study, we presented a neonate with soft tissue damage due to acyclovir extravasation. CASE REPORT: A female newborn (Iranian, Asian) with gestational age 37+2 weeks and breech presentation was born by Cesarean delivery from a mother with a recent history of Herpes simplex virus (HSV) infection (Yas Women's Hospital, Tehran, Iran). Intravenous administration of acyclovir was initiated through a peripheral catheter inserted on the dorsal side of the left hand. A few minutes after the second dose, the patient showed a diffused firm swelling, local discoloration, and induration in the dorsum of the hand. The peripheral catheter was removed immediately. Hyaluronidase was injected subcutaneously in five different regions around the catheterization site. Intermittent limb elevation and cold compression (for 10 minutes) were applied. Serial follow-ups and examinations were performed hourly to check limb inflammation, ischemia, and compartment syndrome. The limb swelling and discoloration significantly improved 4 hours after the second dose of hyaluronidase. CONCLUSION: Early diagnosis of acyclovir extravasation and immediate management could prevent severe complications in neonates. Further studies are needed to suggest a standard approach and treatment protocol for acyclovir extravasation.


Assuntos
Aciclovir , Antivirais , Extravasamento de Materiais Terapêuticos e Diagnósticos , Humanos , Aciclovir/efeitos adversos , Aciclovir/administração & dosagem , Aciclovir/uso terapêutico , Feminino , Recém-Nascido , Antivirais/efeitos adversos , Herpes Simples/tratamento farmacológico , Hialuronoglucosaminidase/administração & dosagem
4.
Clin Exp Med ; 24(1): 119, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38833206

RESUMO

Patients with hematologic malignancies (HMs) are at a significantly higher risk of contracting COVID-19 and experiencing severe outcomes compared to individuals without HMs. This heightened risk is influenced by various factors, including the underlying malignancy, immunosuppressive treatments, and patient-related factors. Notably, immunosuppressive regimens commonly used for HM treatment can lead to the depletion of B cells and T cells, which is associated with increased COVID-19-related complications and mortality in these patients. As the pandemic transitions into an endemic state, it remains crucial to acknowledge and address the ongoing risk for individuals with HMs. In this review, we aim to summarize the current evidence to enhance our understanding of the impact of HMs on COVID-19 risks and outcomes, identify particularly vulnerable individuals, and emphasize the need for specialized clinical attention and management. Furthermore, the impaired immune response to COVID-19 vaccination observed in these patients underscores the importance of implementing additional mitigation strategies. This may include targeted prophylaxis and treatment with antivirals and monoclonal antibodies as indicated. To provide practical guidance and considerations, we present two illustrative cases to highlight the real-life challenges faced by physicians caring for patients with HMs, emphasizing the need for individualized management based on disease severity, type, and the unique circumstances of each patient.


Assuntos
COVID-19 , Neoplasias Hematológicas , Humanos , COVID-19/complicações , COVID-19/imunologia , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/terapia , SARS-CoV-2/imunologia , Masculino , Antivirais/uso terapêutico , Imunossupressores/uso terapêutico , Imunossupressores/efeitos adversos , Pessoa de Meia-Idade , Feminino
5.
Influenza Other Respir Viruses ; 18(6): e13311, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38840301

RESUMO

In September 2023, France was one of the first countries that started a national immunisation campaign with nirsevimab, a new monoclonal antibody against respiratory syncytial virus (RSV). Using data from a network of paediatric intensive care units (PICUs), we aimed to estimate nirsevimab effectiveness against severe cases of RSV bronchiolitis in France. We conducted a case-control study based on the test-negative design and included 288 infants reported by 20 PICUs. We estimated nirsevimab effectiveness at 75.9% (48.5-88.7) in the main analysis and 80.6% (61.6-90.3) and 80.4% (61.7-89.9) in two sensitivity analyses. These real-world estimates confirmed the efficacy observed in clinical studies.


Assuntos
Hospitalização , Unidades de Terapia Intensiva Pediátrica , Infecções por Vírus Respiratório Sincicial , Humanos , França/epidemiologia , Infecções por Vírus Respiratório Sincicial/tratamento farmacológico , Lactente , Unidades de Terapia Intensiva Pediátrica/estatística & dados numéricos , Estudos de Casos e Controles , Masculino , Feminino , Hospitalização/estatística & dados numéricos , Vírus Sincicial Respiratório Humano/efeitos dos fármacos , Anticorpos Monoclonais Humanizados/uso terapêutico , Antivirais/uso terapêutico , Bronquiolite/tratamento farmacológico , Bronquiolite/virologia , Bronquiolite Viral/tratamento farmacológico , Bronquiolite Viral/virologia , Resultado do Tratamento
6.
PLoS One ; 19(6): e0298254, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38843201

RESUMO

BACKGROUND: In randomized controlled trials, Nirmatrelvir/ritonavir (NMV/r) and Molnupiravir (MPV) reduced the risk of severe/fatal COVID-19 disease. Real-world data are limited, particularly studies directly comparing the two agents. METHODS: Using the VA National COVID-19 database, we identified previously uninfected, non-hospitalized individuals with COVID-19 with ≥1 risk factor for disease progression who were prescribed either NMV/r or MPV within 3 days of a positive test. We used inverse probability of treatment weights (IPTW) to account for providers' preferences for a specific treatment. Absolute risk difference (ARD) with 95% confidence intervals were determined for those treated with NMV/r vs. MPV. The primary outcome was hospitalization or death within 30 days of treatment prescription using the IPTW approach. Analyses were repeated using propensity-score matched groups. RESULTS: Between January 1 and November 30, 2022, 9,180 individuals were eligible for inclusion (6,592 prescribed NMV/r; 2,454 prescribed MPV). The ARD for hospitalization/death for NMV/r vs MPV was -0.25 (95% CI -0.79 to 0.28). There was no statistically significant difference in ARD among strata by age, race, comorbidities, or symptoms at baseline. Kaplan-Meier curves did not demonstrate a difference between the two groups (p-value = 0.6). Analysis of the propensity-score matched cohort yielded similar results (ARD for NMV/r vs. MPV -0.9, 95% CI -2.02 to 0.23). Additional analyses showed no difference for development of severe/critical/fatal disease by treatment group. CONCLUSION: We found no significant difference in short term risk of hospitalization or death among at-risk individuals with COVID-19 treated with either NMV/r or MPV.


Assuntos
Antivirais , Tratamento Farmacológico da COVID-19 , COVID-19 , Citidina , Progressão da Doença , Hospitalização , Hidroxilaminas , Leucina , Ritonavir , SARS-CoV-2 , Humanos , Masculino , Feminino , Ritonavir/uso terapêutico , Pessoa de Meia-Idade , Hidroxilaminas/uso terapêutico , Citidina/análogos & derivados , Citidina/uso terapêutico , COVID-19/mortalidade , COVID-19/epidemiologia , Antivirais/uso terapêutico , Leucina/análogos & derivados , Leucina/uso terapêutico , Idoso , SARS-CoV-2/isolamento & purificação , Prolina/análogos & derivados , Prolina/uso terapêutico , Indóis/uso terapêutico , Adulto , Pandemias , Fatores de Risco , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/mortalidade , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/mortalidade , Pneumonia Viral/virologia , Betacoronavirus , Lactamas , Nitrilas
7.
Arch Dermatol Res ; 316(6): 325, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38822848

RESUMO

Treating plantar warts is still a challenging problem with a long list of diverse treatment options that none of them seems to be definitive. To evaluate the effectiveness of intralesional acyclovir versus intralesional Hepatitis-B vaccine (HBV) in treatment of multiple resistant plantar warts. Forty-eight patients with resistant plantar warts completed the study with no dropouts. They were randomized into 3 groups; group(A) receiving intralesional HBV, group (B) receiving intralesional acyclovir and group (C) receiving intralesional saline as a control group over 5 biweekly sessions or until wart clearance. Clinical outcome was assessed through sequential digital lesion photographing upon each visit. Treatment related adverse reactions were recorded. 43.8%, 37.5% & 18.7% of Groups A, B &C respectively showed a complete response. pain was obvious in 100% and 56.3% of cases receiving intralesional acyclovir and HBV respectively. Up to the 6 month follow up period, none of the complete responders in all groups returned with a recurrence. Both acyclovir and HBV showed comparable efficacy and seem to be promising options for treating plantar warts being safe, affordable, and theoretically safe in immunocompromised cases.


Assuntos
Aciclovir , Antivirais , Vacinas contra Hepatite B , Injeções Intralesionais , Verrugas , Humanos , Verrugas/tratamento farmacológico , Verrugas/terapia , Aciclovir/administração & dosagem , Aciclovir/efeitos adversos , Masculino , Feminino , Adulto , Antivirais/administração & dosagem , Antivirais/uso terapêutico , Resultado do Tratamento , Adulto Jovem , Vacinas contra Hepatite B/administração & dosagem , Adolescente , Pessoa de Meia-Idade
8.
Microb Cell Fact ; 23(1): 163, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38824527

RESUMO

BACKGROUND: Type I interferons (IFN-I)-a group of cytokines with immunomodulatory, antiproliferative, and antiviral properties-are widely used as therapeutics for various cancers and viral diseases. Since IFNs are proteins, they are highly susceptible to degradation by proteases and by hydrolysis in the strong acid environment of the stomach, and they are therefore administered parenterally. In this study, we examined whether the intestinal bacterium, enteropathogenic Escherichia coli (EPEC), can be exploited for oral delivery of IFN-Is. EPEC survives the harsh conditions of the stomach and, upon reaching the small intestine, expresses a type III secretion system (T3SS) that is used to translocate effector proteins across the bacterial envelope into the eukaryotic host cells. RESULTS: In this study, we developed an attenuated EPEC strain that cannot colonize the host but can secrete functional human IFNα2 variant through the T3SS. We found that this bacteria-secreted IFN exhibited antiproliferative and antiviral activities similar to commercially available IFN. CONCLUSION: These findings present a potential novel approach for the oral delivery of IFN via secreting bacteria.


Assuntos
Escherichia coli Enteropatogênica , Sistemas de Secreção Tipo III , Escherichia coli Enteropatogênica/metabolismo , Humanos , Sistemas de Secreção Tipo III/metabolismo , Interferon-alfa/metabolismo , Antivirais/farmacologia , Antivirais/metabolismo , Interferon alfa-2/metabolismo , Proliferação de Células/efeitos dos fármacos
9.
Nat Commun ; 15(1): 4855, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38844458

RESUMO

Hepatitis E virus (HEV) is a long-neglected RNA virus and the major causative agent of acute viral hepatitis in humans. Recent data suggest that HEV has a very heterogeneous hypervariable region (HVR), which can tolerate major genomic rearrangements. In this study, we identify insertions of previously undescribed sequence snippets in serum samples of a ribavirin treatment failure patient. These insertions increase viral replication while not affecting sensitivity towards ribavirin in a subgenomic replicon assay. All insertions contain a predicted nuclear localization sequence and alanine scanning mutagenesis of lysine residues in the HVR influences viral replication. Sequential replacement of lysine residues additionally alters intracellular localization in a fluorescence dye-coupled construct. Furthermore, distinct sequence patterns outside the HVR are identified as viral determinants that recapitulate the enhancing effect. In conclusion, patient-derived insertions can increase HEV replication and synergistically acting viral determinants in and outside the HVR are described. These results will help to understand the underlying principles of viral adaptation by viral- and host-sequence snatching during the clinical course of infection.


Assuntos
Vírus da Hepatite E , Hepatite E , Ribavirina , Replicação Viral , Replicação Viral/genética , Vírus da Hepatite E/genética , Vírus da Hepatite E/fisiologia , Vírus da Hepatite E/efeitos dos fármacos , Humanos , Hepatite E/virologia , Hepatite E/tratamento farmacológico , Ribavirina/farmacologia , Mutagênese Insercional , Antivirais/farmacologia , RNA Viral/genética , Genoma Viral , Replicon/genética
10.
Rev Med Virol ; 34(4): e2551, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38849982

RESUMO

This systematic review and meta-analysis aimed to compare the effectiveness and safety of azvudine versus nirmatrelvir/ritonavir (Paxlovid) in treating coronavirus disease 2019 (COVID-19). The researchers conducted searches on PubMed, Cochrane Library, Web of Science, medRxiv, and Google Scholar until January 2024. The Cochrane risk of bias tool was utilised to evaluate the quality of the included studies, and data analysis was performed using Comprehensive Meta-Analysis software. Thirteen studies, including 4949 patients, were analysed. The meta-analysis results showed no significant difference between the azvudine and Paxlovid groups in terms of mortality rate (odds rate [OR] = 0.84, 95% confidence interval [CI]: 0.59-1.21), negative polymerase chain reaction (PCR) conversion time (standard mean difference [SMD] = 1.52, 95% CI: -1.07-4.11), and hospital stay (SMD = -0.39, 95% CI: -1.12-0.33). However, a significant difference was observed between the two groups in terms of intensive care unit admission (OR = 0.42, 95% CI: 0.23-0.75) and the need for mechanical ventilation (OR = 0.61, 95% CI: 0.44-0.86) in favour of azvudine. The incidence of adverse events in the azvudine group was significantly lower (OR = 0.66, 95% CI: 0.43-0.99). The certainty of evidence was rated as low and moderate. Azvudine and Paxlovid demonstrated similar effectiveness in reducing mortality rates, negative PCR conversion time and hospital stay. However, azvudine showed better effectiveness in improving other outcomes. Regarding the level of certainty of evidence, further research is needed to validate or challenge these results.


Assuntos
Antivirais , Tratamento Farmacológico da COVID-19 , Combinação de Medicamentos , Ritonavir , SARS-CoV-2 , Humanos , Antivirais/uso terapêutico , Antivirais/efeitos adversos , Antivirais/administração & dosagem , SARS-CoV-2/efeitos dos fármacos , Ritonavir/uso terapêutico , Ritonavir/administração & dosagem , Ritonavir/efeitos adversos , COVID-19/mortalidade , COVID-19/virologia , Lopinavir/uso terapêutico , Lopinavir/efeitos adversos , Lopinavir/administração & dosagem , Resultado do Tratamento
11.
J Clin Apher ; 39(3): e22131, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38850077

RESUMO

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is a zoonotic infectious disease caused by the severe fever with thrombocytopenia syndrome virus (SFTSV). Endemic in East Asia, SFTS is characterized by an exceptionally high mortality rate. Presently, there is no established treatment for SFTS, particularly for patients in critical condition. In this study, we collected and analyzed laboratory and clinical data from 92 critically ill patients with SFTS treated at Weihai Municipal Hospital between 2019 and 2022. We hope that our study will provide some hints for the treatment of critically ill patients with SFTS. METHODS: A total of 92 critically ill patients with SFTS were included in this study. Of these patients, 45 received treatment with therapeutic plasma exchange (TPE) and ribavirin (referred to as the TPE group), while the remaining patients received only ribavirin (referred to as the non-TPE group). Clinical and laboratory parameters were analyzed retrospectively. RESULTS: The results showed significant improvements in multiple laboratory parameters following treatment with TPE and ribavirin, including white blood cell and neutrophil count, lactate dehydrogenase, creatine kinase isoenzyme-MB, prothrombin time, activated partial thromboplastin time, D-Dimer, serum sodium and copies of virus genomes. The combination of TPE with ribavirin demonstrated a significant reduction in mortality rates, with a mortality rate of 20.0% in the TPE group compared to 40.4% in the non-TPE group (P = 0.033). CONCLUSIONS: Our findings suggest that critically ill patients with SFTS who received TPE and ribavirin experienced improvements in both clinical and laboratory parameters. These results indicate that TPE combined with ribavirin may represent a promising novel therapeutic approach for managing critically ill patients with SFTS. However, comparative studies of large sample size or randomized clinical trials are warranted to confirm the effectiveness of this combination therapy in the treatment of severe SFTS cases.


Assuntos
Estado Terminal , Troca Plasmática , Ribavirina , Febre Grave com Síndrome de Trombocitopenia , Humanos , Ribavirina/uso terapêutico , Troca Plasmática/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , Febre Grave com Síndrome de Trombocitopenia/terapia , Febre Grave com Síndrome de Trombocitopenia/tratamento farmacológico , Antivirais/uso terapêutico , Adulto , Terapia Combinada
12.
Arch Dermatol Res ; 316(6): 314, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38822909

RESUMO

Herpes zoster (HZ) is rare in healthy children, but more prevalent in those with leukemia. Optimal timing of chemotherapy reinitiation after HZ treatment is challenging because chemotherapy suppresses immunity and increases risk of HZ relapse. We aimed to optimize the timing of chemotherapy reinitiation after HZ therapy in children with leukemia. The study included 31 children with acute leukemia and HZ infection. General information, clinical symptoms, laboratory test results, duration of HZ treatment, and prognosis were compared with those of children with leukemia alone. Correlation analysis was performed for 20 children who restarted chemotherapy after HZ treatment. Of 31 children with leukemia and HZ, 67.74% had lesions at multiple sites. The median time from chemotherapy initiation to HZ onset was 14.1 (1.5-29.5) months. Among 27 children included in the follow-up, there was one case of HZ relapse. After excluding children who did not continue chemotherapy after HZ treatment, the median interval between completion of HZ therapy and chemotherapy reinitiation in the remaining 20 children was 8.00 (- 3 to 27) days. Lymphocyte counts (LY#) on restarting chemotherapy correlated inversely with HZ lesion healing time (p < 0.05). LY# at the time of HZ onset were lower than those pre- and post-onset, and lower than those in the control group (p < 0.05). In conclusion, children with leukemia have a good HZ prognosis, but an increased risk of HZ recurrence. LY# at the time of chemotherapy reinitiation may be a useful indicator for selecting the optimal interval between antiviral therapy completion and chemotherapy reinitiation.


Assuntos
Antivirais , Herpes Zoster , Leucemia , Humanos , Herpes Zoster/tratamento farmacológico , Criança , Masculino , Feminino , Pré-Escolar , Antivirais/uso terapêutico , Antivirais/administração & dosagem , Contagem de Linfócitos , Adolescente , Leucemia/tratamento farmacológico , Leucemia/complicações , Prognóstico , Fatores de Tempo , Estudos Retrospectivos , Lactente
13.
J Med Virol ; 96(6): e29723, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38828911

RESUMO

Hepatitis B virus (HBV) can be completely suppressed after antiviral treatment; however, some patients with chronic hepatitis B (CHB) exhibit elevated alanine aminotransferase (ALT) levels and sustained disease progression. This study provides novel insights into the mechanism and potential predictive biomarkers of persistently elevated ALT (PeALT) in patients with CHB after complete viral inhibition. Patients having CHB with undetectable HBV DNA at least 12 months after antiviral treatment were enrolled from a prospective, observational cohort. Patients with PeALT and persistently normal ALT (PnALT) were matched 1:1 using propensity score matching. Correlations between plasma metabolites and the risk of elevated ALT were examined using multivariate logistic regression. A mouse model of carbon tetrachloride-induced liver injury was established to validate the effect of key differential metabolites on liver injury. Of the 1238 patients with CHB who achieved complete viral suppression, 40 (3.23%) had PeALT levels during follow-up (median follow-up: 2.42 years). Additionally, 40 patients with PnALT levels were matched as controls. Ser-Phe-Ala, Lys-Ala-Leu-Glu, 3-methylhippuric acid, 3-methylxanthine, and 7-methylxanthine were identified as critical differential metabolites between the two groups and independently associated with PeALT risk. Ser-Phe-Ala and Lys-Ala-Leu-Glu levels could be used to discriminate patients with PeALT from those with PnALT. Furthermore, N-acetyl- l-methionine (NALM) demonstrated the strongest negative correlation with ALT levels. NALM supplementation alleviated liver injury and hepatic necrosis induced by carbon tetrachloride in mice. Changes in circulating metabolites may contribute to PeALT levels in patients with CHB who have achieved complete viral suppression after antiviral treatment.


Assuntos
Alanina Transaminase , Antivirais , Biomarcadores , Hepatite B Crônica , Humanos , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/sangue , Hepatite B Crônica/virologia , Masculino , Feminino , Alanina Transaminase/sangue , Antivirais/uso terapêutico , Adulto , Estudos Prospectivos , Pessoa de Meia-Idade , Biomarcadores/sangue , Animais , Camundongos , Vírus da Hepatite B , Resposta Viral Sustentada , DNA Viral/sangue , Modelos Animais de Doenças , Fígado/patologia , Fígado/virologia , Carga Viral
14.
ASAIO J ; 70(6): 546-552, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38829573

RESUMO

Drug treatments for coronavirus disease 2019 (COVID-19) dramatically improve patient outcomes, and although extracorporeal membrane oxygenation (ECMO) has significant use in these patients, it is unknown whether ECMO affects drug dosing. We used an ex vivo adult ECMO model to measure ECMO circuit effects on concentrations of specific COVID-19 drug treatments. Three identical ECMO circuits used in adult patients were set up. Circuits were primed with fresh human blood (temperature and pH maintained within normal limits). Three polystyrene jars with 75 ml fresh human blood were used as controls. Remdesivir, GS-441524, nafamostat, and tocilizumab were injected in the circuit and control jars at therapeutic concentrations. Samples were taken from circuit and control jars at predefined time points over 6 h and drug concentrations were measured using validated assays. Relative to baseline, mean (± standard deviation [SD]) study drug recoveries in both controls and circuits at 6 h were significantly lower for remdesivir (32.2% [±2.7] and 12.4% [±2.1], p < 0.001), nafamostat (21.4% [±5.0] and 0.0% [±0.0], p = 0.018). Reduced concentrations of COVID-19 drug treatments in ECMO circuits is a clinical concern. Remdesivir and nafamostat may need dose adjustments. Clinical pharmacokinetic studies are suggested to guide optimized COVID-19 drug treatment dosing during ECMO.


Assuntos
Monofosfato de Adenosina , Alanina , Tratamento Farmacológico da COVID-19 , Oxigenação por Membrana Extracorpórea , Oxigenação por Membrana Extracorpórea/métodos , Humanos , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Monofosfato de Adenosina/farmacocinética , Alanina/análogos & derivados , Alanina/farmacocinética , Alanina/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/farmacocinética , Antivirais/farmacocinética , Antivirais/uso terapêutico , Guanidinas/farmacocinética , Guanidinas/uso terapêutico , Benzamidinas , COVID-19/terapia , SARS-CoV-2 , Adenosina/análogos & derivados
15.
Ann Med ; 56(1): 2361843, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38830017

RESUMO

BACKGROUND: Literature on the safety of remdesivir in hospitalized COVID-19 patients with severe renal impairment is limited. We aimed to investigate the safety and effectiveness of remdesivir in this population. METHODS: We conducted a retrospective cohort study of adult hospitalized COVID-19 patients who received remdesivir between April 2022 and October 2022. Outcomes were compared between estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 and ≥30 mL/min/1.73 m2 groups. The primary safety outcomes were acute kidney injury (AKI) and bradycardia, while the primary effectiveness outcomes included mortality in COVID-19-dedicated wards and hospital mortality. Secondary outcomes included laboratory changes, disease progression, and recovery time. RESULTS: A total of 1,343 patients were recruited, with 307 (22.9%) in the eGFR <30 group and 1,036 (77.1%) in the eGFR ≥30 group. Patients with an eGFR <30 had higher risks of AKI (adjusted hazard ratio [aHR] 2.92, 95% CI 1.93-4.44) and hospital mortality (aHR 1.47, 95% CI 1.06-2.05) but had comparable risks of bradycardia (aHR 1.15, 95% CI 0.85-1.56) and mortality in dedicated wards (aHR 1.43, 95% CI 0.90-2.28) than patients with an eGFR ≥30. Risk of disease progression was higher in the eGFR <30 group (adjusted odds ratio 1.62, 95% CI 1.16-2.26). No difference between the two groups in laboratory changes and recovery time. CONCLUSIONS: Hospitalized COVID-19 patients receiving remdesivir with severe renal impairment had an increased risk of AKI, hospital mortality, and COVID-19 disease progression compared to patients without severe renal impairment.


Assuntos
Injúria Renal Aguda , Monofosfato de Adenosina , Alanina , Antivirais , Tratamento Farmacológico da COVID-19 , Taxa de Filtração Glomerular , Mortalidade Hospitalar , Hospitalização , SARS-CoV-2 , Humanos , Alanina/análogos & derivados , Alanina/uso terapêutico , Alanina/efeitos adversos , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Monofosfato de Adenosina/efeitos adversos , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Antivirais/uso terapêutico , Antivirais/efeitos adversos , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/epidemiologia , Hospitalização/estatística & dados numéricos , COVID-19/complicações , COVID-19/mortalidade , Resultado do Tratamento , Insuficiência Renal/epidemiologia , Bradicardia/induzido quimicamente , Bradicardia/epidemiologia , Adulto
16.
BMC Infect Dis ; 24(1): 556, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38831304

RESUMO

BACKGROUND: Herpes simplex encephalitis (HSE) is an important central nervous infection with severe neurological sequelae. The aim of this study was to describe clinical characteristic and outcomes of patients with HSE in Vietnam. METHODS: This was a retrospective study of 66 patients with herpes simplex encephalitis who admitted to the National Hospital for Tropical Diseases, Hanoi, Vietnam from 2018 to 2021. The detection of herpes simplex virus (HSV) in cerebrospinal fluid was made by the real-time PCR assay. We reported the clinical manifestation on admission and evaluated clinical outcomes at the hospital discharge by modified Rankin Scale (mRS). Multivariate logistic regression analysis was used to analyze the independent risk factors of severe outcomes. RESULTS: Of the 66 patients with laboratory confirmed HSE, the median age was 53 years (IQR 38-60) and 44 patients (69.7%) were male. The most common manifestations included fever (100%), followed by the consciousness disorder (95.5%). Other neurological manifestation were seizures (36.4%), memory disorders (31.8%), language disorders (19.7%) and behavioral disorders (13.6%). Conventional magnetic resonance imaging (MRI) showed 93.8% patients with temporal lobe lesions, followed by abnormalities in insula (50%), frontal lobe (34.4%) and 48.4% of patients had bilateral lesions. At discharge, 19 patients (28.8%) completely recovered, 15 patients (22.7%) had mild sequelae, 28 patients (42.4%) had moderate to severe sequelae. Severe neurological sequelae were memory disorders (55.8%), movement disorders (53.5%), language disorders (30.2%). Multivariate logistic regression analysis showed that Glasgow score decrement at admission, seizures, and time duration from onset of symptoms to the start of Acyclovir treatment > 4 days were independent factors associated with severe outcomes in HSE patients. CONCLUSION: Glasgow score decrement, seizures and delay treatment with Acyclovir were associated with the poor outcome of patients with HSE.


Assuntos
Encefalite por Herpes Simples , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Vietnã/epidemiologia , Adulto , Encefalite por Herpes Simples/tratamento farmacológico , Encefalite por Herpes Simples/virologia , Encefalite por Herpes Simples/epidemiologia , Antivirais/uso terapêutico , Simplexvirus/isolamento & purificação , Simplexvirus/genética , Fatores de Risco , Imageamento por Ressonância Magnética , Aciclovir/uso terapêutico , Resultado do Tratamento
17.
J Coll Physicians Surg Pak ; 34(6): 659-666, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38840347

RESUMO

OBJECTIVE: To evaluate the effect of favipiravir administered to diabetic and non-diabetic COVID-19 patients on the QT/QTc interval. STUDY DESIGN: Analytical study. Place and Duration of the Study: Republic of Turkey, Ministry of Health, State Hospital, Corlu, Tekirdag, Turkiye, from March to September 2021. METHODOLOGY: Electrocardiogram (ECG) analysis was performed on all participants (n=180) divided into four groups. Group 1 included only healthy volunteers. Group 2 included only cases diagnosed with T2DM. Group 3 included only severe acute respiratory syndrome coronavirus-2 (SARS-Cov-2) cases. Group 4 included cases diagnosed with both SARS and T2DM. Favipiravir was administered only to the cases in Group 3 and Group 4. In the cases that were administered favipiravir, the QT/QTc interval was calculated and recorded at different time intervals on the first and fifth days of the therapy. The difference between groups was determined by Tukeye's test after ANOVA. Pearson's correlation test was used to determine whether there was a linear relationship between two numericals. The alpha significance value was determined to be <0.05 in all statistical analyses. RESULTS: When all groups were compared, it was seen that both QT and QTc values ​​increased in Groups 3 and 4, which were administered favipiravir (p <0.05). Favipiravir may cause an increased risk of ventricular and atrial arrhythmias. CONCLUSION: Favipiravir may cause QT interval prolongation, particularly in SARS-Cov-2 patients diagnosed with T2DM. KEY WORDS: COVID-19, Drug-induced long QT syndrome, Intra-infarct haemorrhage; Favipiravir, Type 2 diabetes mellitus.


Assuntos
Amidas , Antivirais , Tratamento Farmacológico da COVID-19 , COVID-19 , Diabetes Mellitus Tipo 2 , Eletrocardiografia , Síndrome do QT Longo , Pirazinas , SARS-CoV-2 , Humanos , Pirazinas/uso terapêutico , Pirazinas/efeitos adversos , Amidas/uso terapêutico , Amidas/efeitos adversos , Masculino , Feminino , Pessoa de Meia-Idade , Diabetes Mellitus Tipo 2/tratamento farmacológico , Antivirais/uso terapêutico , Antivirais/efeitos adversos , COVID-19/complicações , Síndrome do QT Longo/induzido quimicamente , Adulto , Turquia , Idoso
18.
Front Cell Infect Microbiol ; 14: 1407261, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38846354

RESUMO

SARS-CoV-2 is the causative virus of the devastating COVID-19 pandemic that results in an unparalleled global health and economic crisis. Despite unprecedented scientific efforts and therapeutic interventions, the fight against COVID-19 continues as the rapid emergence of different SARS-CoV-2 variants of concern and the increasing challenge of long COVID-19, raising a vast demand to understand the pathomechanisms of COVID-19 and its long-term sequelae and develop therapeutic strategies beyond the virus per se. Notably, in addition to the virus itself, the replication cycle of SARS-CoV-2 and clinical severity of COVID-19 is also governed by host factors. In this review, we therefore comprehensively overview the replication cycle and pathogenesis of SARS-CoV-2 from the perspective of host factors and host-virus interactions. We sequentially outline the pathological implications of molecular interactions between host factors and SARS-CoV-2 in multi-organ and multi-system long COVID-19, and summarize current therapeutic strategies and agents targeting host factors for treating these diseases. This knowledge would be key for the identification of new pathophysiological aspects and mechanisms, and the development of actionable therapeutic targets and strategies for tackling COVID-19 and its sequelae.


Assuntos
COVID-19 , Interações Hospedeiro-Patógeno , SARS-CoV-2 , Replicação Viral , Humanos , COVID-19/virologia , SARS-CoV-2/patogenicidade , Antivirais/uso terapêutico , Interações entre Hospedeiro e Microrganismos
19.
Sci Rep ; 14(1): 13130, 2024 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-38849372

RESUMO

Dengue virus is a single positive-strand RNA virus that is composed of three structural proteins including capsid, envelope, and precursor membrane while seven non-structural proteins (NS1, NS2A, NS2B, NS3A, NS3B, NS4, and NS5). Dengue is a viral infection caused by the dengue virus (DENV). DENV infections are asymptomatic or produce only mild illness. However, DENV can occasionally cause more severe cases and even death. There is no specific treatment for dengue virus infections. Therapeutic peptides have several important advantages over proteins or antibodies: they are small in size, easy to synthesize, and have the ability to penetrate the cell membranes. They also have high activity, specificity, affinity, and less toxicity. Based on the known peptide inhibitor, the current study designs peptide inhibitors for dengue virus envelope protein using an alanine and residue scanning technique. By replacing I21 with Q21, L14 with H14, and V28 with K28, the binding affinity of the peptide inhibitors was increased. The newly designed peptide inhibitors with single residue mutation improved the binding affinity of the peptide inhibitors. The inhibitory capability of the new promising peptide inhibitors was further confirmed by the utilization of MD simulation and free binding energy calculations. The molecular dynamics simulation demonstrated that the newly engineered peptide inhibitors exhibited greater stability compared to the wild-type peptide inhibitors. According to the binding free energies MM(GB)SA of these developed peptides, the first peptide inhibitor was the most effective against the dengue virus envelope protein. All peptide derivatives had higher binding affinities for the envelope protein and have the potential to treat dengue virus-associated infections. In this study, new peptide inhibitors were developed for the dengue virus envelope protein based on the already reported peptide inhibitor.


Assuntos
Antivirais , Vírus da Dengue , Dengue , Peptídeos , Vírus da Dengue/efeitos dos fármacos , Peptídeos/química , Peptídeos/farmacologia , Dengue/tratamento farmacológico , Dengue/virologia , Antivirais/farmacologia , Antivirais/química , Antivirais/uso terapêutico , Humanos , Desenho de Fármacos , Simulação de Dinâmica Molecular , Proteínas do Envelope Viral/antagonistas & inibidores , Proteínas do Envelope Viral/metabolismo , Proteínas do Envelope Viral/química , Simulação por Computador , Ligação Proteica
20.
Sci Rep ; 14(1): 13150, 2024 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-38849399

RESUMO

The ongoing COVID-19 pandemic continues to pose significant challenges worldwide, despite widespread vaccination. Researchers are actively exploring antiviral treatments to assess their efficacy against emerging virus variants. The aim of the study is to employ M-polynomial, neighborhood M-polynomial approach and QSPR/QSAR analysis to evaluate specific antiviral drugs including Lopinavir, Ritonavir, Arbidol, Thalidomide, Chloroquine, Hydroxychloroquine, Theaflavin and Remdesivir. Utilizing degree-based and neighborhood degree sum-based topological indices on molecular multigraphs reveals insights into the physicochemical properties of these drugs, such as polar surface area, polarizability, surface tension, boiling point, enthalpy of vaporization, flash point, molar refraction and molar volume are crucial in predicting their efficacy against viruses. These properties influence the solubility, permeability, and bio availability of the drugs, which in turn affect their ability to interact with viral targets and inhibit viral replication. In QSPR analysis, molecular multigraphs yield notable correlation coefficients exceeding those from simple graphs: molar refraction (MR) (0.9860), polarizability (P) (0.9861), surface tension (ST) (0.6086), molar volume (MV) (0.9353) using degree-based indices, and flash point (FP) (0.9781), surface tension (ST) (0.7841) using neighborhood degree sum-based indices. QSAR models, constructed through multiple linear regressions (MLR) with a backward elimination approach at a significance level of 0.05, exhibit promising predictive capabilities highlighting the significance of the biological activity I C 50 (Half maximal inhibitory concentration). Notably, the alignment of predicted and observed values for Remdesivir's with obs p I C 50 = 6.01 ,pred p I C 50 = 6.01 ( p I C 50 represents the negative logarithm of I C 50 ) underscores the accuracy of multigraph-based QSAR analysis. The primary objective is to showcase the valuable contribution of multigraphs to QSPR and QSAR analyses, offering crucial insights into molecular structures and antiviral properties. The integration of physicochemical applications enhances our understanding of factors influencing antiviral drug efficacy, essential for combating emerging viral strains effectively.


Assuntos
Antivirais , Tratamento Farmacológico da COVID-19 , Relação Quantitativa Estrutura-Atividade , Antivirais/farmacologia , Antivirais/química , Antivirais/uso terapêutico , Humanos , SARS-CoV-2/efeitos dos fármacos , COVID-19/virologia , Modelos Lineares
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