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The spillovers of β-coronaviruses in humans and the emergence of SARS-CoV-2 variants highlight the need for broad coronavirus countermeasures. We describe five monoclonal antibodies (mAbs) cross-reacting with the stem helix of multiple β-coronavirus spike glycoproteins isolated from COVID-19 convalescent individuals. Using structural and functional studies we show that the mAb with the greatest breadth (S2P6) neutralizes pseudotyped viruses from three different subgenera through inhibition of membrane fusion and delineate the molecular basis for its cross-reactivity. S2P6 reduces viral burden in hamsters challenged with SARS-CoV-2 through viral neutralization and Fc-mediated effector functions. Stem helix antibodies are rare, oftentimes of narrow specificity and can acquire neutralization breadth through somatic mutations. These data provide a framework for structure-guided design of pan-β-coronavirus vaccines eliciting broad protection.

Though an acute kidney injury (AKI) episode is associated with an increased risk of chronic kidney disease (CKD), the mechanisms determining the transition from acute to irreversible chronic injury are not well understood. To extend our understanding of renal repair, and its limits, we performed a detailed molecular characterization of a murine ischemia/reperfusion injury (IRI) model for 12 months after injury. Together, the data comprising RNA-sequencing (RNA-seq) analysis at multiple time points, histological studies, and molecular and cellular characterization of targeted gene activity provide a comprehensive profile of injury, repair, and long-term maladaptive responses following IRI. Tubular atrophy, interstitial fibrosis, inflammation, and development of multiple renal cysts were major long-term outcomes of IRI. Progressive proximal tubular injury tracks with de novo activation of multiple Krt genes, including Krt20, a biomarker of renal tubule injury. RNA-seq analysis highlights a cascade of temporal-specific gene expression patterns related to tubular injury/repair, fibrosis, and innate and adaptive immunity. Intersection of these data with human kidney transplant expression profiles identified overlapping gene expression signatures correlating with different stages of the murine IRI response. The comprehensive characterization of incomplete recovery after ischemic AKI provides a valuable resource for determining the underlying pathophysiology of human CKD.