About: Screening of FDA-Approved Drugs for Inhibitors of Japanese Encephalitis Virus Infection

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About: Screening of FDA-Approved Drugs for Inhibitors of Japanese Encephalitis Virus Infection Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : covidontheweb.inria.fr associated with source document(s)

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Screening of FDA-Approved Drugs for Inhibitors of Japanese Encephalitis Virus Infection
Creator	Wang, Wei Liu, Yang Xiao, Gengfu Guo, Jiao Wang, Shaobo Zhang, Leike Wang, Peilin
Source	PMC
abstract	Japanese encephalitis virus (JEV), an arthropod-borne flavivirus, is a major cause of acute viral encephalitis in humans. No approved drug is available for the specific treatment of JEV infections, and the available vaccines are not effective against all clinical JEV isolates. In the study described here, a high-throughput screening of an FDA-approved drug library for inhibitors of JEV was performed. Five hit drugs that inhibited JEV infection with a selective index of >10 were identified. The antiviral activities of these five hit drugs against other flavivirus, including Zika virus, were also validated. As three of the five hit drugs were calcium inhibitors, additional types of calcium inhibitors that confirmed that calcium is essential for JEV infection, most likely during viral replication, were utilized. Adaptive mutant analysis uncovered that replacement of Q130, located in transmembrane domain 3 of the nonstructural NS4B protein, which is relatively conserved in flaviviruses, with R or K conferred JEV resistance to manidipine, a voltage-gated Ca(2+) channel (VGCC) inhibitor, without an apparent loss of the viral growth profile. Furthermore, manidipine was indicated to protect mice against JEV-induced lethality by decreasing the viral load in the brain, while it abrogated the histopathological changes associated with JEV infection. This study provides five antiflavivirus candidates and identifies cytoplasmic calcium to be a novel antiviral target for the treatment of JEV infection. The findings reported here provide therapeutic possibilities for combating infections caused by flaviviruses. IMPORTANCE No approved therapy for the treatment of Japanese encephalitis virus infection is currently available. Repurposing of approved drugs would accelerate the development of a therapeutic stratagem. In this study, we screened a library of FDA-approved drugs and identified five hit drugs, especially calcium inhibitors, exerting antiflavivirus activity that blocked viral replication. The in vivo efficacy and toxicity of manidipine were investigated with a mouse model of JEV infection, and the viral target was identified by generating an adaptive mutant.
has issue date	2017-10-13(xsd:dateTime)
bibo:doi	10.1128/jvi.01055-17
bibo:pmid	28814523
has license	cc-by
sha1sum (hex)	1bd2f6497996fc0fccd8dffd7f84846d3d36f964
schema:url	https://doi.org/10.1128/jvi.01055-17
resource representing a document's title	Screening of FDA-Approved Drugs for Inhibitors of Japanese Encephalitis Virus Infection
has PubMed Central identifier	PMC5640845
has PubMed identifier	28814523
schema:publication	J Virol
resource representing a document's body	covid:1bd2f6497996fc0fccd8dffd7f84846d3d36f964#body_text
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