Small Molecule Antiviral for Paramyxoviruses

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Introduction: Paramyxoviruses cause respiratory tract infections. These include viral diseases such as mumps, measles, and parainfluenza infections and are the most common viral infections leading to admission to pediatric intensive care units (PICUs) in the United States. Human parainfluenza virus (HPIV) infections also can be a threat to immune-compromised adults including transplant recipients and the elderly, with mortality rates reaching up to 75% in certain scenarios. Currently, there is no vaccine to prevent or specific antiviral to treat HPIV infections. Given that pediatric, immuno-compromised and elderly populations are commonly at risk for developing complication, an effective therapy for HPIV likely requires a stronger safety profile than traditional antiviral therapeutic approaches directed toward host factors or ribonucleoside analogs can provide. Therefore, an anti-paramyxoviral drug with a broad-spectrum capacity and a tight safety profile is critically needed. Technology: Georgia State University researchers and their collaborator have identified a small molecule that possesses broad-spectrum activity against diverse paramyxoviruses including both HPIV3 and measles virus. GSU researchers performed a high-throughput screening of more than 140,000 compounds and found one allosteric inhibitor of HPIV3 polymerase, GHP-88309. The inhibitory activity of GHP-88309 showed broadened efficacy against other members of the respirovirus genus (HPIV1, Sendai virus (SeV)) as well as morbilliviruses (MeV, canine distemper virus) in vitro. When the compound was orally administrated to the SeV mouse surrogate model of HPIV3 at 48 hours post-infection, it was well-tolerated and provided protection. Taken together this indicates GHP-88309 and other compounds from its family exhibit potential to work as a well-behaved broad-spectrum allosteric antiviral.