About: Development of antibody-based assays for high throughput discovery and mechanistic study of antiviral agents against yellow fever virus

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About: Development of antibody-based assays for high throughput discovery and mechanistic study of antiviral agents against yellow fever virus Goto Sponge NotDistinct Permalink

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type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Development of antibody-based assays for high throughput discovery and mechanistic study of antiviral agents against yellow fever virus
Creator	Zhang, Lin Chang, Jinhong Guo, Ju-Tao Hong, Seon-Hui Zhang, L Ma, Julia Rice, Charles Gao, Zhao Macdonald, Margaret Gao, Z Jurado, Andrea Jurado, J Macdonald, C Rice, J.-T
Source	Elsevier; Medline; PMC
abstract	Abstract Despite the availability of a highly effective yellow fever virus (YFV) vaccine, outbreaks of yellow fever frequently occur in Africa and South America with significant mortality, highlighting the pressing need for antiviral drugs to manage future outbreaks. To support the discovery and development of antiviral drugs against YFV, we characterized a panel of rabbit polyclonal antibodies against the three YFV structural proteins and five non-structural proteins and demonstrated these antibody reagents in conjunction with viral RNA metabolic labeling, double-stranded RNA staining and membrane floatation assays as powerful tools for investigating YFV polyprotein processing, replication complex formation, viral RNA synthesis and high throughput discovery of antiviral drugs. Specifically, the proteolytic processing of the viral polyprotein can be analyzed by Western blot assays. The predominant nuclear localization of NS5 protein as well as the relationship between intracellular viral non-structural protein distribution and foci of YFV RNA replication can be revealed by immunofluorescence staining and membrane flotation assays. Using an antibody against YFV NS4B protein as an example, in-cell western and high-content imaging assays have been developed for high throughput discovery of antiviral agents. A synergistic antiviral effect of an YFV NS4B-targeting antiviral agent BDAA and a NS5 RNA-dependent RNA polymerase inhibitor (Sofosbuvir) was also demonstrated with the high-content imaging assay. Apparently, the antibody-based assays established herein not only facilitate the discovery and development of antiviral agents against YFV, but also provide valuable tools to dissect the molecular mechanism by which the antiviral agents inhibit YFV replication.
has issue date	2020-08-14(xsd:dateTime)
bibo:doi	10.1016/j.antiviral.2020.104907
bibo:pmid	32798604
has license	els-covid
sha1sum (hex)	d6b38b3c2e21802b3ff2e9ef43f072347470f534
schema:url	https://doi.org/10.1016/j.antiviral.2020.104907
resource representing a document's title	Development of antibody-based assays for high throughput discovery and mechanistic study of antiviral agents against yellow fever virus
has PubMed Central identifier	PMC7426275
has PubMed identifier	32798604
schema:publication	Antiviral Research
resource representing a document's body	covid:d6b38b3c2e21802b3ff2e9ef43f072347470f534#body_text
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