NEW YORK (Reuters Health) – Using a novel high-throughput screening assay, a team of scientists has discovered that two highly virulent viruses are susceptible in vitro to the antimalarial drug chloroquine. Their findings appear in a report released early by the Journal of Virology, set for print publication in the May 1 issue.
“Nipah and Hendra viruses are newly emerging zoonoses that cause encephalitis in humans, with fatality rates of up to 75%,” Dr. Anne Moscona, at Weill Cornell Medical College, New York, and co-authors explain. The viruses can also cause late-onset disease and persistent or delayed neurological sequelae. Infection is transmitted from fruit bats, pigs, and horses, as well as person-to-person.
Ordinarily, testing on such lethal pathogens requires high level biocontainment. Dr. Moscona’s group developed relatively safe “pseudotyped” viruses in which the Nipah and Hendra envelope glycoproteins (including binding and fusion proteins) were attached to a recombinant vesicular stomatitis virus lacking its attachment protein. They point out that the resulting virions are noninfectious.
They first screened more than 23,000 compounds against the pseudotyped viruses, of which 184 (including chloroquine) showed no cytotoxicity and greater than 50% inhibition.
They then focused their research on chloroquine, based on its safety profile and its clinical use at the dosage shown to have in vitro antiviral potency against Hendra virus.
They found that increasing concentrations of chloroquine appeared to inactivate the virus and thereby reduce the amount of infectious virus released from infected cells.
Dr. Moscona and her associates propose that chloroquine’s “mechanism of action, inhibition of a cellular enzyme required for virus infectivity, has the added advantage of being unlikely to elicit resistance, since the drug targets a host, rather than a viral enzyme.”
J Virol 2009.