SARS-CoV-2 is the cause of a pandemic with growing global mortality. Using comprehensive identification of RNA-binding proteins by mass spectrometry (ChIRP-MS), we identified 309 host proteins that bind the SARS-CoV-2 RNA during active infection. Integration of this data with ChIRP-MS data from three other RNA viruses defined viral specificity of RNA-host protein interactions. Targeted CRISPR screens revealed that the majority of functional RNA-binding proteins protect the host from virus-induced cell death, and comparative CRISPR screens across seven RNA viruses revealed shared and SARS-specific antiviral factors. Finally, by combining the RNA-centric approach and functional CRISPR screens, we demonstrated a physical and functional connection between SARS-CoV-2 and mitochondria, highlighting this organelle as a general platform for antiviral activity. Altogether, these data provide a comprehensive catalog of functional SARS-CoV-2 RNA-host protein interactions, which may inform studies to understand the host-virus interface and nominate host pathways that could be targeted for therapeutic benefit.

Disorders of the cornea are responsible for a significant portion of preventable blindness worldwide. Various types of corneal transplantation procedures have successfully restored vision in many individuals; however, they carry the risk of graft failure due to immune rejection, endothelial cell dysfunction, infections and limbal stem cell deficiency. Thus, regenerative therapies of the cornea serve as promising alternatives or adjunct therapies. With improved understanding of limbal stem cell function and advancement in limbal stem cell culture technologies, major progress has been made in the in vivo and ex vivo cell-based therapies for treatment of corneal diseases. In this review, we summarize the recent developments achieved in cell-based therapeutics to target corneal epithelial, stromal, and endothelial cell disorders.

Alzheimer disease (AD) is characterized by plaques and tangles, including calcium dysregulation and glycated products produced by reactive carbonyl compounds. AD brains have increased glyoxalase I (GLO1), a major scavenger of inflammatory carbonyl compounds, at early, but not later, stages of disease. Calcium dysregulation includes calcium leak from phosphorylated ryanodine receptor 2 (pS2808-RyR2), seen in aged macaques and AD mouse models, but the downstream consequences of calcium leak remain unclear. Here, we show that chronic calcium leak is associated with increased GLO1 expression and activity. In macaques, we found age-related increases in GLO1 expression in the prefrontal cortex (PFC), correlating with pS2808-RyR2, and localized to dendrites and astrocytes. To examine the relationship between GLO1 and RyR2, we used S2808D-RyR2 mutant mice exhibiting chronic calcium leak through RyR2, and found increased GLO1 expression and activity in the PFC and hippocampus as early as 1 month and as late as 21 months of age, with a bell-shaped aging curve. These aged S2808D-RyR2 mice demonstrated impaired working memory. As with macaques, GLO1 was expressed in astrocytes and neurons. Proteomics data generated from S2808D-RyR2 synaptosomes confirmed GLO1 upregulation. Altogether, these data suggest potential association between GLO1 and chronic calcium leak, providing resilience in early stages of aging.