Development of an Antiviral Screening Protocol: One-Stone-Two-Birds


As prophylactic therapies and vaccines against viral infections continue to improve, drug resistant strains are continuing to arise; therefore it is imperative to develop new therapeutics against these diseases. For highly pathogenic viruses, such as Ebola and H5N1 influenza virus, the need for antivirals is even more urgent due to limited therapeutics against these viruses. Furthermore, the high pathogenicity of such viruses often makes it difficult to work with such agents. In this report, we describe a protocol called “One-stone-two-birds” which provides a safe and efficient screening system to identify anti-flu (entry) and anti-HIV (replication) activities. Using plant extracts as an example, we demonstrate the utility of this protocol in antiviral screening.

Prophylactic therapeutics and vaccines continue to be critical strategies to fight the spread of viral infections. For example, vaccines are the primary method of controlling the spread of influenza A virus. Due to the ability of this virus to constantly acquire genetic changes, new vaccines are formulated and produced annually. These vaccines are based on the most widely spread strains from the previous year which are predicted to be most prevalent in the coming flu season. In addition to vaccines, several prophylactic therapies are available, such as Tamiflu and Relenza, which can be taken after infection to halt the spread of the virus. These antivirals provide a treatment option post-infection, however, not all influenza A viruses respond to these treatments and some strains are resistant. Thus new antiviral therapies are urgently needed.

One impediment to developing antiviral therapeutics for highly pathogenic viruses, such as H5N1 influenza and Ebola, which require enhanced BSL-3 and 4 containment, respectively, is the safety concerns. To circumvent this problem, we have established a surrogate pseudotyping system, referred to as the One-stone-two-birds approach here, which allows us to study the antiviral activity targeted against both the HA-mediated entry mechanism of influenza virus and the replication process of HIV. In this study, we evaluated and identified plant extracts which demonstrated antiviral activities by this approach.

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Robert har