Yellow fever, caused by the mosquito-transmitted yellow fever virus (YFV), is a potentially fatal disease that has plagued humans for centuries. The 17D vaccine, raised against an attenuated strain of YFV, has been available for more than 80 years and provides excellent protection. Nevertheless, significant vulnerability in the world population persists even with vaccination and vector control programs, as exemplified by recent outbreaks in Africa and South America. In addition, the existence of the vaccine may have slowed the impetus to identify therapeutic antivirals to treat symptomatic cases of yellow fever in unvaccinated people. Thus, research into YFV biology and candidate agents that disrupt the viral life cycle remain a world public health priority.
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In their recent Antiviral Research study, Gao et al. describe the development of antibody-based assays to facilitate high-throughput discovery of anti-YFV agents. To do this, the researchers first performed an exhaustive analysis on a series of research antibodies from GeneTex that target the three structural and five of the nonstructural proteins encoded by the YFV genome. They used the antibodies for both biochemical and cell biology assays to explore YFV polyprotein processing, replication complex organization, and viral RNA synthesis. The anti-NS4B antibody (GTX134030) was then incorporated into in-cell western and high-content imaging assays that revealed a synergistic antiviral effect of the compounds BDAA and Sofosbuvir, which target NS4B and the NS5 RNA polymerase, respectively. These findings demonstrate how antibody-based assays can not only expedite screening for antiviral agents against YFV, but also provide insight into the mechanistic basis of their inhibitory actions.
GeneTex is a leader in the production of reliable reagents for the study of an array of viral pathogens, including flaviviruses, influenza viruses, enteroviruses, and coronaviruses (i.e., MERS-CoV, SARS-CoV, and SARS-CoV-2), among others. The GeneTex team’s top priority is to create reagents that perform well in the hands of researchers. We are particularly gratified by the impressive results generated by Gao et al. using our YFV antibodies.
Gao et al. Antiviral Res. 2020 Oct; 182: 104907.