Chloroquine Shown to Be Effective Against Emerging Viral Diseases

The well-known anti-malaria drug chloroquine has been shown to be an effective treatment for two emerging and deadly viruses, Nipah virus (NiV) and Hendra virus (HeV). These are emerging zoonotic paramyxoviruses that cause encephalitis in humans, with fatality rates of up to 75%

Investigators from Weill Cornell Medical College (New York, NY, USA) identified chloroquine's antiviral potential using a novel high-throughput screening (HTS) assay. The assay was based on a series of "pseudotype” viruses, hybrid viruses that displayed the surface structure of the deadly virus strain but lacking that virus' genome. This allowed the investigators to work in a regular laboratory rather than in the type of biohazard containment facility normally required for handling these types of pathogens. The assay simulated multicycle replication and thus identified inhibitors that targeted several stages of the viral life cycle.

Results published in the March 4, 2009, online edition of the Journal of Virology revealed that chloroquine inhibited infection with live HeV and NiV at a concentration lower than the plasma concentrations present in humans receiving chloroquine treatment for malaria. The mechanism for chloroquine's antiviral action is likely to be inhibition of cathepsin L, a cellular enzyme that is essential for processing of the viral fusion glycoprotein and maturation of newly budding virions. Without this processing step, virions are not infectious.

"Chloroquine stands a good chance of making it through the development process in time to prevent further outbreaks of these deadly infections,” said senior author Dr. Anne Moscona, professor of pediatrics, microbiology, and immunology at Weill Cornell Medical College. "The fact that chloroquine is safe and widely used in humans means that it may bypass the usual barriers associated with drug development and move quickly into clinical trials.”

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Weill Cornell Medical College