The current justified furor regarding epidemic preparedness has emphasized an unmet need for therapeutic strategies that lead to rapid implementation. The prompt identification and sequencing of the COVID-19 genome has prompted herculean efforts to rapidly design and produce vaccines and other antiviral interventions. Nevertheless, the generalized availability of such therapeutics will be markedly out of phase with the first wave of this disease. 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, COVID-19, 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 in the upcoming months. Herein we expand upon this strategy and its scientific underpinning wherein 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 that the known mechanistic information on NPC1 could be utilized within the context of COVID-19 and associated candidate therapeutics.
