Therapeutics for RSV Infection

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Introduction: Discovered in 1965, Respiratory syncytial virus (RSV), a single-stranded orthopneumovirus, is the global leading cause of severe lower respiratory tract infections in infants younger than 6 months. Almost all children are infected by age 2, and it is one of the leading causes of morbidity and mortality in children younger than 5 years. It is estimated that in 2015 alone, for children under 5 years, such infections resulted in 3.2 million hospital admissions and 59,600 deaths worldwide. However, RSV is not only a problem for the young, but is a substantial threat to the health of the elderly and the immunocompromised as well. There are currently no vaccines available to prevent RSV infections; other therapeutic options have been limited, and in some cases discontinued, due to complex administration schedules, limited protection windows, high cost and somewhat variable efficacy. It is therefore an urgent priority to develop improved, safe, and effective therapeutics capable of both treating active RSV infections and being used prophylactically to potentially prevent infections. Technology: Georgia State University researchers and collaborators at Emory University have discovered innovative inhibitors of certain pneumovirus protein-ligand interactions using fragment-based drug discovery and structure-activity relationship investigation by nuclear magnetic resonance. Using these approaches, a previously unexplored mechanism for RSV drug development was identified focused on exploiting a highly druggable protein-protein-interaction between RSV RNA-dependent RNA polymerase (RdRp) and the nucleocapsid protein-encapsidated viral genome. Through a high-throughput anti-RSV screen of a 57,000-compound library, a presumptive first-in-class chemical scaffold that selectively blocks activity of the RdRp complex has been identified.