1. Inhibition of hepatitis E virus replication by peptide-conjugated morpholino oligomers.
- Author
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Nan Y, Ma Z, Kannan H, Stein DA, Iversen PI, Meng XJ, and Zhang YJ
- Subjects
- Capsid Proteins analysis, Cell Line, Hepatitis E virus physiology, Hepatocytes virology, Humans, Microbial Sensitivity Tests, RNA, Viral analysis, Viral Load, Antiviral Agents pharmacology, Drug Carriers metabolism, Hepatitis E virus drug effects, Morpholinos pharmacology, Oligonucleotides, Antisense pharmacology, Peptides metabolism, Virus Replication drug effects
- Abstract
Hepatitis E virus (HEV) infection is a cause of hepatitis in humans worldwide and has been associated with a case-fatality rate of up to 30% in pregnant women. Recently, persistent and chronic HEV infections have been recognized as a serious clinical problem, especially in immunocompromised individuals. To date, there are no FDA-approved HEV-specific antiviral drugs. In this study, we evaluated antisense peptide-conjugated morpholino oligomers (PPMO) designed against HEV genomic sequences as potential HEV-specific antiviral compounds. Two genetically-distinct strains of human HEV, genotype 1 Sar55 and genotype 3 Kernow-C1, isolated from patients with acute and chronic hepatitis, respectively, were used to evaluate inhibition of viral replication by PPMO in liver cells. The anti-HEV PPMO produced a significant reduction in the levels of HEV RNA and capsid protein, indicating effective inhibition of HEV replication. PPMO HP1, which targets a highly conserved sequence in the start site region of ORF1, was also effective against the genotype 3 Kernow-C1 strain in stably-infected HepG2/C3A liver cells. The antiviral activity observed was specific, dose-responsive and potent, suggesting that further exploration of PPMO HP1 as a potential HEV-specific antiviral agent is warranted., (Copyright © 2015 Elsevier B.V. All rights reserved.)
- Published
- 2015
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