Article ; Online: Repurposing of artesunate, an antimalarial drug, as a potential inhibitor of hepatitis E virus.
2023 Volume 168, Issue 5, Page(s) 147
Abstract: Hepatitis E virus (HEV) is endemic in several developing countries of Africa and Asia. It mainly causes self-limiting waterborne infections, in either sporadic or outbreak form. Recently, HEV was shown to cause chronic infections in immunosuppressed ... ...
Abstract | Hepatitis E virus (HEV) is endemic in several developing countries of Africa and Asia. It mainly causes self-limiting waterborne infections, in either sporadic or outbreak form. Recently, HEV was shown to cause chronic infections in immunosuppressed individuals. Ribavirin and interferon, the current off-label treatment options for hepatitis E, have several side effects. Hence, there is a need for new drugs. We evaluated the antimalarial drug artesunate (ART) against genotype 1 HEV (HEV-1) and HEV-3 using a virus-replicon-based cell culture system. ART exhibited 59% and 43% inhibition of HEV-1 and HEV-3, respectively, at the highest nontoxic concentration. Computational molecular docking analysis showed that ART can bind to the helicase active site (affinity score, -7.4 kcal/mol), indicating its potential to affect ATP hydrolysis activity. An in vitro ATPase activity assay of the helicase indeed showed 24% and 55% inhibition at 19.5 µM (EC |
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MeSH term(s) | Female ; Pregnancy ; Animals ; Humans ; Hepatitis E virus/genetics ; Artesunate/pharmacology ; Artesunate/therapeutic use ; Antimalarials/pharmacology ; Drug Repositioning ; Molecular Docking Simulation ; Virus Replication ; Hepatitis E/drug therapy ; RNA-Dependent RNA Polymerase/genetics ; Adenosine Triphosphate |
Chemical Substances | Artesunate (60W3249T9M) ; Antimalarials ; RNA-Dependent RNA Polymerase (EC 2.7.7.48) ; Adenosine Triphosphate (8L70Q75FXE) |
Language | English |
Publishing date | 2023-04-28 |
Publishing country | Austria |
Document type | Journal Article |
ZDB-ID | 7491-3 |
ISSN | 1432-8798 ; 0304-8608 |
ISSN (online) | 1432-8798 |
ISSN | 0304-8608 |
DOI | 10.1007/s00705-023-05770-1 |
Database | MEDical Literature Analysis and Retrieval System OnLINE |
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