The in vitro Evaluation of the Activity of COVID-19 Antiviral Drugs Against Adenovirus

PURPOSE: 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. METHODS: The 50% effective concentrations (EC(50)) 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. RESULTS: The range of mean in vitro EC(50) 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(50) concentrations than CDV for 6 of 7 HAdV types. Potency increases with lower EC(50) concentrations. CONCLUSION: 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.