>> Wednesday, May 09, 2012
Research team led by Michael J. Holtzman, MD, from Washington University, US, has recently reported the possibility of novel strategy to find small molecules that can enhance the host defense system against a broad range of viruses. The compounds were tested for their ability to increase the interferon signaling pathway (IFN-pathway) which mediates the host defense against a wide range of viruses. The team has conducted the cell-based high throughput screening of 2240 compounds which led to 64 hit compounds with significant interferon-stimulated response element ISRE) activity being idarubicin hydrochloride the most potent. Idarubicin, an anthracycline, is used as anti-cancer agent. DNA intercalation and topoisomerase II inhibition is responsible for its anti-cancer activity. To confirm that increased ISRE activity by idarubicin is independant of topoisomerase inhibitory effect, the team tested other three potent topoisomerase inhibitors (Etoposide, Hu-0331, and ICRF-193) for the ISRE activity. Interestingly, they found these compounds did not show significant increase in ISRE activity. Instead, two of them (etoposide and Hu-0331) caused decreased ISRE activity.
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Authors concluded that they validated the phenotypic screening strategy to identify small molecules that enhance the activity of the type I IFN signaling pathway and consequently improve antiviral host defense. They believed that this approach should thereby prove useful to discover drugs with activity against a broad range of viruses as well as other conditions (e.g., multiple sclerosis, melanoma) where the efficacy of IFN treatment might benefit from enhancing IFN signaling.
As you know, idarubicin, like other anticancer agents, has severe side effects; it cannot be easily used for antiviral purpose. But these findings have provided a new path in the antiviral drug discovery which enables the screening of more compounds to find potent one with less toxicity and side effects.
Source: Plos one