Romanowski Eric G, Yates Kathleen A, Romanowski John E, Shanks Robert M Q, Kowalski Regis P
The Charles T. Campbell Ophthalmic Microbiology Laboratory, UPMC Eye Center, Ophthalmology and Visual Sciences Research Center, Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Clin Ophthalmol. 2021 Dec 22;15:4787-4793. doi: 10.2147/OPTH.S340576. eCollection 2021.
Presently, there is no approved antiviral therapy for adenovirus (HAdV) ocular infections. During the COVID-19 pandemic, increased attention has been focused on antiviral treatments. Remdesivir, hydroxychloroquine, ivermectin, and umifenovir (Arbidol) have been touted as potential antiviral treatments for COVID-19. The goal of the current study was to determine whether these potential COVID-19 antivirals produce in vitro antiviral activity against a panel of ocular adenovirus types.
The 50% effective concentrations (EC) of remdesivir (REM), hydroxychloroquine (HCQ), ivermectin (IVM), umifenovir (UMF) and cidofovir (CDV) (positive antiviral control) were determined for the human HAdV types HAdV3, HAdV4, HAdV5, HAdV7a, HAdV8, HAdV19/64 and HAdV37 using standard plaque-reduction assays in A549 cells.
The range of mean in vitro EC concentrations for each antiviral across the range of HAdV types is as follows: The positive antiviral control, CDV, ranged from 0.47 to 9.62 µM; REM ranged from 0.21 to 11.27 µM; UMF ranged from 3.72 to 64.8 µM; IVR ranged from 2.60 to 201.3 µM; and HCQ was >10 µM for all Ad types because of toxicity to the A549 cells. REM produced lower EC concentrations than CDV for 6 of 7 HAdV types. Potency increases with lower EC concentrations.
REM demonstrated anti-adenovirus activity in a range similar to that demonstrated by cidofovir. UMF and IVR demonstrated larger ranges of antiviral activity than CDV and REM across the panel of HAdV types. The anti-adenovirus activity of HCQ could not be determined due to cytotoxicity. Further investigation of REM, UMF, and IVR as antivirals for adenovirus is indicated.
目前，尚无获批用于腺病毒（HAdV）眼部感染的抗病毒疗法。在新冠疫情期间，抗病毒治疗受到了更多关注。瑞德西韦、羟氯喹、伊维菌素和乌米芬诺尔（阿比多尔）被吹捧为新冠病毒的潜在抗病毒治疗药物。本研究的目的是确定这些潜在的新冠病毒抗病毒药物是否对一组眼部腺病毒类型具有体外抗病毒活性。
使用标准蚀斑减少试验在A549细胞中测定瑞德西韦（REM）、羟氯喹（HCQ）、伊维菌素（IVM）、乌米芬诺尔（UMF）和西多福韦（CDV）（阳性抗病毒对照）对人HAdV 3型、HAdV 4型、HAdV 5型、HAdV 7a型、HAdV 8型、HAdV 19/64型和HAdV 37型的50%有效浓度（EC）。
每种抗病毒药物在一系列HAdV类型中的平均体外EC浓度范围如下：阳性抗病毒对照CDV为0.47至9.62µM；REM为0.21至11.27µM；UMF为3.72至64.8µM；IVR为2.60至201.3µM；由于对A549细胞有毒性，所有腺病毒类型的HCQ均>10µM。对于7种HAdV类型中的6种，REM产生的EC浓度低于CDV。效力随EC浓度降低而增加。
REM表现出的抗腺病毒活性范围与西多福韦相似。在一组HAdV类型中，UMF和IVR表现出比CDV和REM更大范围的抗病毒活性。由于细胞毒性，无法确定HCQ的抗腺病毒活性。表明需要进一步研究REM、UMF和IVR作为腺病毒抗病毒药物的情况。
