Pharmacological Inhibitors of VPS34

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Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an enveloped positive-sense RNA virus of the beta-coronavirus genus causing the most significant pandemic across the world in the last century. Repurposing drugs developed for other diseases/clinical conditions can only provide a shortcut to antiviral development for coronavirus infections. However, the requirements of the viral life cycle and the virus replication mechanism are still not well understood, causing paucity of appropriate therapeutic strategies necessary to combat the severity and continuing evolution of this pandemic. Technology: A Georgia State University researcher has developed methods of screening for therapeutic agents, along with strategies for using those agents, for potential treatment, reduction and prevention of coronavirus infections. VPS34 is a multifunctional protein involved in autophagy and membrane trafficking. Because of the significant role of membrane rearrangements in coronavirus replication, the researcher discovered that compounds targeting VPS34 and fatty acid synthase are potent SARS-CoV-2 inhibitors. VPS34 strongly impaired SARS-CoV-2 replication in vitro. By identifying these potential host factors and lipid metabolism pathways that are critical for SARS-CoV-2 multiplication, novel mechanistic insights have been introduced that may aid in the potential development of therapeutics for the treatment of COVID-19.