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May 20, 2014

Raising Hopes for the Treatment of MERS

  • Several teams of scientists report the identification of a number of existing pharmaceutical drugs and compounds under development that may offer effective therapies against Middle East Respiratory Syndrome (MERS).

    In one study, researchers screened a library of 290 pharmaceutical drugs, either FDA-approved or in advanced clinical development, for antiviral activity against the MERS coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus (SARS-CoV) in cell culture. They found 27 compounds that were active against both viruses including some cancer drugs and antipsychotics.

    "Repurposing of approved pharmaceutical drugs for new indications presents an attractive alternative to the normal paradigm of huge library screening against a specific viral enzyme," says Matthew Frieman, Ph.D., of the University of Maryland Medical School and an author on one of the studies. "Given development times and manufacturing requirements for new products, repurposing of existing drugs is likely the best solution to rapidly identify therapeutics for outbreaks due to emerging viruses."

    Scientists from the NIH, the U.S. Army Medical Research Institute of Infectious Diseases, and Cambridge, MA-based Zalicus worked with Dr. Frieman on the study (“Repurposing 1 of clinically developed drugs for treatment of Middle East Respiratory Coronavirus”), which appears in Antimicrobial Agents and Chemotherapy (AAC).

    In a second study in AAC (“Screening of an FDA-approved compound library identifies 7 four small-molecule inhibitors of Middle East respiratory 8 syndrome coronavirus replication in cell culture”), scientists collaborating in the European antiviral research program known as SILVER screened a library of 348 FDA-approved drugs for anti-MERS-CoV activity in cell culture. They identified four compounds that inhibited MERS-CoV, SARS-CoV, and Human Coronavirus 229E at relatively low concentrations. Two of the compounds were also identified by the U.S. study: the antimalarial drug chloroquine and the antipsychotic chlorpromazine.

    "Although their therapeutic potential (alone or in combination) remains to be assessed in animal models, our findings may offer a starting point for treatment of patients infected with zoonotic coronaviruses like MERS-CoV," wrote the investigators who are based at Leiden University Medical Center in the Netherlands, the Rega Institute for Medical Research in Leuven, Belgium, and the Erasmus Medical Center in Rotterdam, the Netherlands. "Although they may not necessarily reduce viral replication to very low levels, a moderate viral load reduction may create a window to mount a protective immune response."

    A third study finds that an experimental compound, previously shown to block SARS-CoV replication, can inhibit replication of two other coronaviruses, MERS-CoV and mouse hepatitis virus.

    "This study shows that it is possible to target multiple coronaviruses through broad-spectrum inhibitors," says corresponding author Stefan Sarafianos, Ph.D., of the Bond Life Sciences Center at the University of Missouri, an author of the study. "This compound could serve as a lead for the development of effective broad-spectrum anticoronavirus drugs."


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