文章基本信息

标题：Development of a Method That Delivers Drugs to Enveloped Viruses
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作者：Insaf Bahrini ; Rikinari Hanayama
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2019
卷号：42
期号：6
页码：977-981
DOI：10.1248/bpb.b18-01000
出版社：The Pharmaceutical Society of Japan
摘要：Hepatitis C virus (HCV) infection leads to chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma in 50–80% of the cases. Interferons (IFNs) and the nucleoside analog ribavirin form the basis of the treatment of this infection but are not considered sufficiently effective and cause several side effects. In this study, we developed a novel viral-specific drug delivery method. Enveloped viruses, including HCV, expose an anionic phospholipid, phosphatidylserine (PS), on their surface to mediate their binding and entry into cells for infection. To target such exposed PS on HCV, we developed a chimeric recombinant protein containing human IFN and mouse lactadherin (also known as milk fat globule epidermal growth factor 8), which binds with high affinity to PS. The IFN–lactadherin fusion protein showed a high binding affinity toward PS and HCV and consequently blocked viral replication in the infected cells more efficiently than conventional IFN. Overall, these data suggest that conjugation with lactadherin facilitates the delivery of any protein drug to PS-exposing enveloped viruses.
关键词：drug delivery;enveloped virus;phosphatidylserine;lactadherin;interferon;viral replication