Antiviral Effects of Curcumin on Adenovirus Replication.

Morgan R Jennings,Robin J Parks

doi:10.3390/microorganisms8101524

Abstract

Human adenovirus (HAdV) is a common pathogen that can cause severe morbidity and mortality in certain populations, including pediatric, geriatric, and immunocompromised patients. Unfortunately, there are no approved therapeutics to combat HAdV infections. Curcumin, the primary curcuminoid compound found in turmeric spice, has shown broad activity as an antimicrobial agent, limiting the replication of many different bacteria and viruses. In this study, we evaluated curcumin as an anti-HAdV agent. Treatment of cells in culture with curcumin reduced HAdV replication, gene expression, and virus yield, at concentrations of curcumin that had little effect on cell viability. Thus, curcumin represents a promising class of compounds for further study as potential therapeutics to combat HAdV infection.

Highlights

Human adenovirus (HAdV) is a non-enveloped, icosahedral, double-stranded DNA virus, capable of infecting ocular [1], respiratory [2], or gastrointestinal tissues [3]
A549 cells were infected with HAdV-5 at an MOI of 10 for 1 h, and incubated in curcumin-containing medium until 8 or 24 hpi
A549 cells were infected with HAdV-5 at an MOI of 10 for 1 h, at which point medium containing 50 μM of curcumin was added

Summary

Introduction

Human adenovirus (HAdV) is a non-enveloped, icosahedral, double-stranded DNA (dsDNA) virus, capable of infecting ocular [1], respiratory [2], or gastrointestinal tissues [3]. Using an assay based on inhibition of cytopathic effect in cells, Hartline et al [15] performed a screen of 16 compounds for efficacy against several different DNA viruses, including HAdV, and identified filociclovir, a nucleoside analogue [18], as effective against HAdV and several other viruses. The degree to which a test compound affects viral gene expression and replication inversely correlates with quantity of RFP present in the treated cells [16]. Using this HTS strategy, we tested the Prestwick library (~1200 compounds, most of which are FDA-approved) for compounds affecting HAdV infection and identified 11 compounds with anti-HAdV activity [16]. We investigated the efficacy of curcumin as an anti-HAdV compound

Materials and Methods

Treatment with Curcumin Reduces HAdV-5 Genome Copy Number within Cells

Treatment with Curcumin Reduces Viral Yield

Continued Exposure to Curcumin is Required to Inhibit HAdV Protein Expression

Infection and Drug Treatments

Immunoblot Analysis

Plaque Assay for Virus Yield

MTS Metabolic Activity Assays

Statistical Analysis

Treatment with Curcumin Reduces HAdV-5 Protein Expression

Treatment with Curcumin Reduces HAdV Types 4 and 7 Protein Levels