کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8523406 | 1557794 | 2018 | 32 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Efficacy of pritelivir and acyclovir in the treatment of herpes simplex virus infections in a mouse model of herpes simplex encephalitis
ترجمه فارسی عنوان
اثربخشی پریتلوویر و آیزکلوویر در درمان عفونت ویروس هرپس سیمپلکس در مدل موش آنسفالیت ساده ی آن
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کلمات کلیدی
درمان ضد ویروسی، مدل موش، آنسفالیت ساده آنفلوآنزا، ترکیبی اثر،
موضوعات مرتبط
علوم زیستی و بیوفناوری
ایمنی شناسی و میکروب شناسی
ویروس شناسی
چکیده انگلیسی
Pritelivir, a helicase-primase inhibitor, has excellent in vitro and in vivo activity against human herpes simplex virus (HSV). Mice lethally infected with HSV type 1 or 2, including acyclovir-resistant strains, were treated 72Â h after infection for 7 days with pritelivir or acyclovir. Both drugs were administered orally twice daily either alone or in combination. Dosages of pritelivir from 0.3 to 30Â mg/kg reduced mortality (PÂ <Â 0.001) against HSV-1, E-377. With an acyclovir resistant HSV-1, 11360, pritelivir at 1 and 3Â mg/kg increased survival (PÂ <Â 0.005). With HSV-2, MS infected mice, all dosages higher than the 0.3Â mg/kg dose of pritelivir were effective (PÂ <Â 0.005). For acyclovir resistant HSV-2, strain 12247, pritelivir dosages of 1-3Â mg/kg significantly improved survival (PÂ <Â 0.0001). Combination therapies of pritelivir at 0.1 or 0.3Â mg/kg/dose with acyclovir (10Â mg/kg/dose) were protective (PÂ <Â 0.0001) when compared to the vehicle treated group against HSV-2, strain MS (in line with previous data using HSV-1). An increased mean days to death (PÂ <Â 0.05) was also observed and was indicative of a potential synergy. Pharmacokinetic studies were performed to determine pritelivir concentrations and a dose dependent relationship was found in both plasma and brain samples regardless of infection status or time of initiation of dosing. In summary, pritelivir was shown to be active when treatment was delayed to 72Â h post viral inoculation and appeared to synergistically inhibit mortality in this model in combination with acyclovir. We conclude pritelivir has potent and resistance-breaking antiviral efficacy with potential for the treatment of potentially life-threatening HSV type 1 and 2 infections, including herpes simplex encephalitis.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Antiviral Research - Volume 149, January 2018, Pages 1-6
Journal: Antiviral Research - Volume 149, January 2018, Pages 1-6
نویسندگان
Debra C. Quenelle, Alexander Birkmann, Thomas Goldner, Tamara Pfaff, Holger Zimmermann, Susanne Bonsmann, Deborah J. Collins, Terri L. Rice, Mark N. Prichard,