AI Article Synopsis
Article Abstract
Introduction: We evaluated the antiviral activities of ribavirin (RBV) and interferon (IFN) alfa as monotherapy and combination therapy against chikungunya virus (CHIKV).
Methods: Vero cells were infected with CHIKV in the presence of RBV and/or IFN alfa, and viral production was quantified by plaque assay. A mathematical model was fit to the data to identify drug interactions for effect. We ran simulations using the best-fit model parameters to predict the antiviral activity associated with clinically relevant regimens of RBV and IFN alfa as combination therapy. The model predictions were validated using the hollow fiber infection model (HFIM) system.
Results: RBV and IFN alfa were effective against CHIKV as monotherapy at supraphysiological concentrations. However, RBV and IFN alfa were highly synergistic for antiviral effect when administered as combination therapy. Simulations with our mathematical model predicted that a standard clinical regimen of RBV plus IFN alfa would inhibit CHIKV burden by 2.5 log10 following 24 hours of treatment. In the HFIM system, RBV plus IFN alfa at clinical exposures resulted in a 2.1-log10 decrease in the CHIKV burden following 24 hours of therapy. These findings validate the prediction made by the mathematical model.
Conclusions: These studies illustrate the promise of RBV plus IFN alfa as a potential therapeutic strategy for the treatment of CHIKV infections.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5034961 | PMC |
| http://dx.doi.org/10.1093/infdis/jiw358 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
[Evaluation of whole blood immunoreactivity].
Khirurgiia (Mosk)
December 2024
Petrovsky National Research Center of Surgery, Moscow, Russia.
To assess cellular immunoreactivity, lipopolysaccharide (LPS), Concanavalin A (Con A), or LPS together with Con A was added to the whole blood for 18 hours. LPS preferentially stimulated release of tumor necrosis factor-alfa (TNF-α), interleukin-6 (IL-6), IL-10 and vascular endothelial growth factor (VEGF) by blood cells, whereas Con A significantly enhanced secretion of interferon-gamma (IFN-gamma) and IL-2. Addition of heparin to blood slightly decreased cellular secretion of IL-2 and VEGF, but not other cytokines.
View Article and Find Full Text PDFPegylated interferon: the who, why, and how.
Hematology Am Soc Hematol Educ Program
December 2024
Hopital Saint-Louis, Paris Cité University, Inserm CIC 1427, Paris, France.
Interferon alpha (IFN-α) is a fascinating molecule with many biological properties yet to be fully understood. Among these properties, several have demonstrated usefulness for targeting malignant cells, including hematopoietic cells from patients with myeloproliferative neoplasms. Indeed, IFN-α has been used for decades across all myeloproliferative neoplasms, but only recently a new form, ropegIFN-α2b, was approved to treat patients with polycythemia vera.
View Article and Find Full Text PDF[HBsAg trajectory and key watersheds towards functional cure of hepatitis B].
Zhonghua Gan Zang Bing Za Zhi
November 2024
Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou510515, China the Institute of Liver Diseases, Guangzhou510515, China.
Chronic hepatitis B virus (HBV) infection remains a pivotal global public health concern. Attaining a functional cure for hepatitis B continues to be a hot and difficult issue that requires immediate attention in clinical practice. There are currently nucleos(t)ide analogues (NAs) that can persistently suppress HBV DNA; however, the functional cure rate of pegylated interferon alfa (PEG-IFN-α) alone or in combination with NAs has not yet met clinical needs.
View Article and Find Full Text PDFPegylated interferon-α2a in cutaneous T-cell lymphoma - a multicenter retrospective data analysis with 70 patients.
J Dtsch Dermatol Ges
November 2024
Department of Dermatology and Venereology, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
Article Synopsis
- Interferon-alpha is crucial for treating cutaneous T-cell lymphomas (CTCL), but the approved version (IFN-α2a) has been unavailable since January 2020, prompting the use of pegylated interferon-α2a (pegIFN-α2a), which is not officially approved for this condition.
- A study involving 70 CTCL patients from twelve German skin centers found a 55.2% overall response rate to pegIFN-α2a, with common adverse effects leading to a 50% discontinuation rate within about 63 weeks.
- The findings suggest that pegIFN-α2a therapy may have similar efficacy and side effects as the discontinued IF
Efficacy of short-term Peg-IFN α-2b treatment in chronic hepatitis B patients with ultra-low HBsAg levels: a retrospective cohort study.
Virol J
September 2024
Department of Infectious Diseases, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150081, Heilongjiang, China.
Purpose: Peginterferon alfa-2b (Peg-IFN α-2b) has demonstrated superior efficacy over nucleos(t)ide analogs (NAs) in the treatment of chronic hepatitis B (CHB), particularly among patients with low levels of hepatitis B surface antigen (HBsAg). This study aims to determine whether patients with ultra-low HBsAg levels (< 200 IU/mL) can achieve significantly higher clinical cure rates with abbreviated courses of Peg-IFN α-2b therapy.
Methods: In this retrospective analysis, CHB patients with HBsAg levels below 200 IU/mL were categorized into a Peg-IFN α-2b group and a control group.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!