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- Title
Ivermectin Inhibits HBV Entry into the Nucleus by Suppressing KPNA2.
- Authors
Nakanishi, Anna; Okumura, Hiroki; Hashita, Tadahiro; Yamashita, Aya; Nishimura, Yuka; Watanabe, Chihiro; Kamimura, Sakina; Hayashi, Sanae; Murakami, Shuko; Ito, Kyoko; Iwao, Takahiro; Ikeda, Akari; Hirose, Tomoyasu; Sunazuka, Toshiaki; Tanaka, Yasuhito; Matsunaga, Tamihide
- Abstract
Hepatitis B virus (HBV) specifically infects human hepatocytes and increases the risks of cirrhosis and liver cancer. Currently, nucleic acid analogs are the main therapeutics for chronic hepatitis caused by HBV infection. Although nucleic acid analogs can eliminate HBV DNA by inhibiting HBV reverse transcriptase, they cannot lead to negative conversion of covalently closed circular DNA (cccDNA) and hepatitis B surface antigen (HBsAg). In this study, we revealed that the antifilarial drug ivermectin suppresses HBV production by a different mechanism from the nucleic acid analog entecavir or Na+ taurocholate co-transporting polypeptide-mediated entry inhibitor cyclosporin A. Ivermectin reduced the levels of several HBV markers, including HBsAg, in HBV-infected human hepatocellular carcinoma cells (HepG2-hNTCP-C4 cells) and humanized mouse hepatocytes (PXB hepatocytes). In addition, ivermectin significantly decreased the expression of HBV core protein and the nuclear transporter karyopherin α2 (KPNA2) in the nuclei of HepG2-hNTCP-C4 cells. Furthermore, depletion of KPNA1–6 suppressed the production of cccDNA. These results suggest that KPNA1–6 is involved in the nuclear import of HBV and that ivermectin suppresses the nuclear import of HBV by inhibiting KPNA2. This study demonstrates the potential of ivermectin as a novel treatment for hepatitis B.
- Subjects
IVERMECTIN; HEPATITIS associated antigen; HEPATITIS B virus; CHRONIC active hepatitis; CIRCULAR DNA; REVERSE transcriptase
- Publication
Viruses (1999-4915), 2022, Vol 14, Issue 11, p2468
- ISSN
1999-4915
- Publication type
Article
- DOI
10.3390/v14112468