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

Abstract

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 (EC₅₀) 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 EC₅₀ 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 EC₅₀ concentrations than CDV for 6 of 7 HAdV types. Potency increases with lower EC₅₀ 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.

Keywords:

• adenovirus
• remdesivir
• ivermectin
• umifenovir
• in vitro
• antiviral

Acknowledgments

The study was supported by The Charles T. Campbell Ophthalmic Microbiology Laboratory, Pittsburgh, PA; NIH CORE Grant for Vision Research EY08098; The Eye & Ear Foundation of Pittsburgh, Pittsburgh, PA; and an unrestricted grant to the University of Pittsburgh Department of Ophthalmology from Research to Prevent Blindness, New York, NY. The Charles T. Campbell Laboratory participated in the design of the study, the conduct of the study, data collection, data management, data analysis, interpretation of the data, preparation, review, and approval of the manuscript. This study was presented at the ARVO 2021 virtual conference as a poster presentation. The abstract was published in Investigative Ophthalmology & Visual Science 2021;62:411.

Disclosure

The authors report no financial interests or conflicts of interest in this work.