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Cell Studies on SARS-CoV-2 Interactions, Pancreatic Progenitor Cell Population

A pair of Cell studies from independent research teams delve into SARS-CoV-2 coronavirus features and interactions with human cell surface receptors. Using cell line, protein interaction and expression, electron microscopy, and other experiments, for example, researchers from the US and France compared coronavirus spike (S) glycoprotein features in the SARS-CoV-2 and SARS-CoV viruses, along with their interactions with the human ACE2 receptor protein. "Our results provide a structural framework to identify conserved and accessible epitopes across S glycoproteins that will support ongoing vaccine design efforts," they write, adding that "elicitation of diverse, polyclonal [antibody] responses might prove key in light of the diversity of viruses circulating in animal reservoirs and in preventing the possible emergence of viral neutralization escape mutants."

A team from Germany and Austria takes a closer look at SARS-CoV-2 coronavirus entry into cells, generating cell line and other evidence suggesting the coronavirus spike protein relies not only on the ACE2 receptor for its entry into cells, but also on a serine protease enzyme called TMPRSS2 for viral spike protein cleavage. The researchers saw hints that the latter spike protein "priming" process might be thwarted to some extent with a protease inhibitor. Their results also pointed to the possibility of trying to tackle the SARS-CoV-2 behind the current pandemic using antibodies from the blood of individuals who recovered from infections with the SARS-CoV virus that emerged nearly two decades ago. "[W]e show that the sera from convalescent SARS patients cross-neutralized SARS-2-S-driven entry," the authors report, noting that these and other findings "reveal important commonalities between SARS-CoV-2 and SARS-CoV infection and identify a potential target for antiviral intervention."

Researchers from China and the Netherlands describe a set of progenitor cells in the mouse pancreas that appear capable of undergoing clonal expansion to produce organoids with islet-like cells. Starting with single-cell RNA sequencing, the team assessed expression profiles in individual cells originating in the adult mouse pancreas, uncovering a population of cells marked by protein C receptor (Procr+). In a series of follow-up experiments, the authors found that the Procr+ progenitor cells were capable of producing four endocrine cell types, and could be selectively expanded to establish glucose-responsive, insulin-secreting islet organoids capable of reversing diabetes symptoms when transplanted into mouse models.