کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5822405 1117941 2013 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
ReviewCuring a viral infection by targeting the host: The example of cyclophilin inhibitors
ترجمه فارسی عنوان
مرور بررسی عفونت ویروسی با هدف قرار دادن میزبان: مثال مهار کننده های سیکلوفیلین
موضوعات مرتبط
علوم زیستی و بیوفناوری ایمنی شناسی و میکروب شناسی ویروس شناسی
چکیده انگلیسی


- Viruses exploit multiple host cell mechanisms for their own replication.
- These mechanisms may serve as targets for antiviral therapy.
- Host-targeted therapies may have a high barrier to resistance.
- Cyclophilin inhibitors have shown promise in curing chronic hepatitis C.
- Cyclophilin inhibitors may potentially be used to treat other viral infections.

Every step of the viral life cycle is dependent on the host, which potentially can be explored for antiviral targets. Historically, however, drug discovery has focused mainly on viral targets, because of their perceived specificity. Efforts to pursue host targets have been largely hampered by concern over potential on-target toxicity, the lack of predictive cell culture and animal models, and the complexity of host-virus interactions. On the other hand, there are distinct advantages of targeting the host, such as creating a high barrier to resistance, providing broad coverage of different genotypes/serotypes and possibly even multiple viruses, and expanding the list of potential targets, when druggable viral targets are limited. Taking hepatitis C virus (HCV) as the example, there are more than 20 inhibitors of the viral protease, polymerase and NS5A protein currently in advanced clinical testing. However, resistance has become a main challenge with these direct-acting antivirals, because HCV, an RNA virus, is notoriously prone to mutation, and a single mutation in the viral target may prevent the binding of an inhibitor, and rendering it ineffective. Host cyclophilin inhibitors have shown promising effects both in vitro and in patients to prevent the emergence of resistance and to cure HCV infection, either alone or in combination with other agents. They are also capable of blocking the replication of a number of other viral pathogens. While the road to developing host-targeting antivirals has been less traveled, and significant challenges remain, delivering the most effective antiviral regimen, which may comprise inhibitors of both host and viral targets, should be well worth the effort.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Antiviral Research - Volume 99, Issue 1, July 2013, Pages 68-77
نویسندگان
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