Stephen Sturley - April 15, 2020

Stephen L. Sturley, "Potential COVID-19 therapeutics from a rare neurodegenerative disease: weaponizing lipid dysregulation to combat SARS-CoV-2 infectivity"

Strategic drug repurposing combined with rapid testing of molecular targets could provide at least a pause in disease progression and aid mitigation. With respect to the current pandemic, SARS-CoV-2, in common with other enveloped viruses (e.g., HIV, Ebola, SARS, and MERS), encounter the endosomal/lysosomal host compartment as a critical step for infection and maturation. A surprisingly key interaction requires engagement of the Niemann-Pick type C1 (NPC1) pathway. This observation prompts the utilization of NPC1 inhibitors as antiviral agents. Fortunately, there are such molecules, in many cases available as generics, that could be rapidly deployed. Given the biological conservation of SARS-CoV-1 and SARS-CoV-2, and the role of the NPC1-dependent late endosome/lysosome lipid pathway in coronavirus infections, we suggest here that known mechanistic information on NPC1 could be utilized to identify existing and future drugs to prevent, ease, and treat COVID-19. (Summary provided by presenter.)