کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5551653 1557798 2017 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Discovery of dapivirine, a nonnucleoside HIV-1 reverse transcriptase inhibitor, as a broad-spectrum antiviral against both influenza A and B viruses
موضوعات مرتبط
علوم زیستی و بیوفناوری ایمنی شناسی و میکروب شناسی ویروس شناسی
پیش نمایش صفحه اول مقاله
Discovery of dapivirine, a nonnucleoside HIV-1 reverse transcriptase inhibitor, as a broad-spectrum antiviral against both influenza A and B viruses
چکیده انگلیسی


- Dapivirine has broad-spectrum influenza antiviral activity against influenza A and B viruses.
- Dapivirine has a high in vitro genetic barrier to drug resistance.
- Dapivirine inhibits the early stage of influenza virus replication by inhibiting the nuclear entry of vRNP.
- Dapivirine shows synergistic influenza antiviral activity with oseltamivir carboxylate.

The emergence of multidrug-resistant influenza viruses poses a persistent threat to public health. The current prophylaxis and therapeutic interventions for influenza virus infection have limited efficacy due to the continuous antigenic drift and antigenic shift of influenza viruses. As part of our ongoing effort to develop the next generation of influenza antivirals with broad-spectrum antiviral activity and a high genetic barrier to drug resistance, in this study we report the discovery of dapivirine, an FDA-approved HIV nonnucleoside reverse transcriptase inhibitor, as a broad-spectrum antiviral against multiple strains of influenza A and B viruses with low micromolar efficacy. Mechanistic studies revealed that dapivirine inhibits the nuclear entry of viral ribonucleoproteins at the early stage of viral replication. As a result, viral RNA and protein synthesis were inhibited. Furthermore, dapivirine has a high in vitro genetic barrier to drug resistance, and its antiviral activity is synergistic with oseltamivir carboxylate. In summary, the in vitro antiviral results of dapivirine suggest it is a promising candidate for the development of the next generation of dual influenza and HIV antivirals.

240

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Antiviral Research - Volume 145, September 2017, Pages 103-113
نویسندگان
, , , , , ,