Abstract
Purpose :
Presently, there is no FDA approved antiviral therapy for the treatment of adenovirus (Ad) ocular infections, the most common ocular viral infection worldwide. During the COVID-19 pandemic, much attention has been placed on several potential antiviral treatments for SARS-CoV-2 infections. Remdesivir, hydroxychloroquine, ivermectin, and umifenovir (Arbidol) have been touted as potential COVID-19 treatments. The goal of the current study was to determine whether these potential COVID-19 antivirals produced in vitro antiviral activity against a panel of ocular adenovirus types.
Methods :
The 50% inhibitory concentrations (IC50) of remdesivir (REM), hydroxychloroquine (HCQ), ivermectin (IVM), and umifenovir (UMF) and cidofovir (CDV) (positive antiviral control) were determined for the human Ad types Ad3, Ad4, Ad5, Ad7a, Ad8, Ad19/64 and Ad37 using standard plaque-reduction assays on A549 cells. Briefly, cells infected with ~100 PFU of the Ad types were treated with final concentrations of the antivirals of 100, 10, 1.0, 0.1, 0.01 and 0.001 µM. After incubation, the numbers of plaques from each virus/drug concentration were counted and the mean IC50 concentrations from 2-3 assays were determined by regression analysis.
Results :
The range of mean in vitro IC50 concentrations for each antiviral across the range of Ad types are as follows: The positive antiviral control, CDV, ranged from 0.47 - 9.62 µM; REM ranged from 0.21 - 11.27 µM; UMF ranged from 3.72 - 64.8 µM; IVR ranged from 2.60 - 201.3 µM; and HCQ was > 10 µM for all Ad types because of toxicity to the A549 cells demonstrated at the 100 µM concentrations. REM produced lower IC50 concentrations than CDV for 5 of 7 Ad types.
Conclusions :
REM demonstrated anti-adenovirus activity in vitro in a range similar to that demonstrated by cidofovir. UMF and IVR demonstrated less antiviral activity than CDV and REM. The anti-adenovirus activity of HCQ could not be accurately determined. Further investigation of REM as an antiviral for adenovirus is indicated.
This is a 2021 ARVO Annual Meeting abstract.