Targeting Lipid Rafts-A Potential Therapy for COVID-19.

COVID-19 is a global pandemic currently in an acute phase of rapid expansion. While public health measures remain the most effective protection strategy at this stage, when the peak passes, it will leave in its wake important health problems. Historically, very few viruses have ever been eradicated. Instead, the virus may persist in communities causing recurrent local outbreaks of the acute infection as well as several chronic diseases that may arise from the presence of a "suppressed" virus or as a consequence of the initial exposure. An ideal solution would be an anti-viral medication that (i) targets multiple stages of the viral lifecycle, (ii) is insensitive to frequent changes of viral phenotype due to mutagenesis, (iii) has broad spectrum, (iv) is safe and (v) also targets co-morbidities of the infection. In this Perspective we discuss a therapeutic approach that owns these attributes, namely "lipid raft therapy." Lipid raft therapy is an approach aimed at reducing the abundance and structural modifications of host lipid rafts or at targeted delivery of therapeutics to the rafts. Lipid rafts are the sites of the initial binding, activation, internalization and cell-to-cell transmission of SARS-CoV-2. They also are key regulators of immune and inflammatory responses, dysregulation of which is characteristic to COVID-19 infection. Lipid raft therapy was successful in targeting many viral infections and inflammatory disorders, and can potentially be highly effective for treatment of COVID-19.

The lysosome: A potential juncture between SARS-CoV-2 infectivity and Niemann-Pick disease type C, with therapeutic implications.

Drug repurposing is potentially the fastest available option in the race to identify safe and efficacious drugs that can be used to prevent and/or treat COVID-19. By describing the life cycle of the newly emergent coronavirus, SARS-CoV-2, in light of emerging data on the therapeutic efficacy of various repurposed antimicrobials undergoing testing against the virus, we highlight in this review a possible mechanistic convergence between some of these tested compounds. Specifically, we propose that the lysosomotropic effects of hydroxychloroquine and several other drugs undergoing testing may be responsible for their demonstrated in vitro antiviral activities against COVID-19. Moreover, we propose that Niemann-Pick disease type C (NPC), a lysosomal storage disorder, may provide new insights into potential future therapeutic targets for SARS-CoV-2, by highlighting key established features of the disorder that together result in an "unfavorable" host cellular environment that may interfere with viral propagation. Our reasoning evolves from previous biochemical and cell biology findings related to NPC, coupled with the rapidly evolving data on COVID-19. Our overall aim is to suggest that pharmacological interventions targeting lysosomal function in general, and those particularly capable of reversibly inducing transient NPC-like cellular and biochemical phenotypes, constitute plausible mechanisms that could be used to therapeutically target COVID-19.