Romanowski Eric G, Hussein Islam T M, Cardinale Steven C, Butler Michelle M, Morin Lucas R, Bowlin Terry L, Yates Kathleen A, Shanks Robert M Q, Kowalski Regis P
The Charles T. Campbell Ophthalmic Microbiology Laboratory, UPMC Eye Center, Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
Microbiotix, Inc., Worcester, MA 01605, USA.
Pharmaceuticals (Basel). 2021 Mar 26;14(4):294. doi: 10.3390/ph14040294.
Presently, there is no FDA- or EMA-approved antiviral for the treatment of human adenovirus (HAdV) ocular infections. This study determined the antiviral activity of filociclovir (FCV) against ocular HAdV isolates in vitro and in the Ad5/NZW rabbit ocular model. The 50% effective concentrations (EC) of FCV and cidofovir (CDV) were determined for several ocular HAdV types using standard plaque reduction assays. Rabbits were topically inoculated in both eyes with HAdV5. On day 1, the rabbits were divided into four topical treatment groups: (1) 0.5% FCV 4x/day × 10 d; (2) 0.1% FCV 4x/day × 10 d; (3) 0.5% CDV 2x/day × 7 d; (4) vehicle 4x/day × 10 d. Eyes were cultured for virus on days 0, 1, 3, 4, 5, 7, 9, 11, and 14. The resulting viral eye titers were determined using standard plaque assays. The mean in vitro EC for FCV against tested HAdV types ranged from 0.50 to 4.68 µM, whereas those treated with CDV ranged from 0.49 to 30.3 µM. In vivo, compared to vehicle, 0.5% FCV, 0.1% FCV, and 0.5% CDV produced lower eye titers, fewer numbers of positive eye cultures, and shorter durations of eye infection. FCV demonstrated anti-adenovirus activity in vitro and in vivo.
目前，尚无经美国食品药品监督管理局（FDA）或欧洲药品管理局（EMA）批准用于治疗人腺病毒（HAdV）眼部感染的抗病毒药物。本研究确定了泛昔洛韦（FCV）在体外以及在Ad5/NZW兔眼部模型中对眼部HAdV分离株的抗病毒活性。使用标准蚀斑减少试验确定了FCV和西多福韦（CDV）对几种眼部HAdV类型的50%有效浓度（EC）。给兔子双眼局部接种HAdV5。在第1天，将兔子分为四个局部治疗组：（1）0.5%FCV，每天4次，共10天；（2）0.1%FCV，每天4次，共10天；（3）0.5%CDV，每天2次，共7天；（4）赋形剂，每天4次，共10天。在第0、1、3、4、5、7、9、11和14天对眼睛进行病毒培养。使用标准蚀斑试验确定所得的眼部病毒滴度。FCV对测试的HAdV类型的体外平均EC范围为0.50至4.68µM，而用CDV治疗的范围为0.49至30.3µM。在体内，与赋形剂相比，0.5%FCV、0.1%FCV和0.5%CDV产生的眼部滴度更低、眼部阳性培养物数量更少且眼部感染持续时间更短。FCV在体外和体内均表现出抗腺病毒活性。
