The main viral protease (3CL pro ) is indispensable for SARS-CoV-2 replication. We delineate the human protein substrate landscape of 3CL pro by TAILS substrate-targeted N-terminomics. We identify >100 substrates in human lung and kidney cells supported by analyses of SARS-CoV-2-infected cells. Enzyme kinetics and molecular docking simulations of 3CL pro engaging substrates reveal how noncanonical cleavage sites, which diverge from SARS-CoV, guide substrate specificity. Cleaving the interactors of essential effector proteins, effectively stranding them from their binding partners, amplifies the consequences of proteolysis. We show that 3CL pro targets the Hippo pathway, including inactivation of MAP4K5, and key effectors of transcription, mRNA processing, and translation. We demonstrate that Spike glycoprotein directly binds galectin-8, with galectin-8 cleavage disengaging CALCOCO2/NDP52 to decouple antiviral-autophagy. Indeed, in post-mortem COVID-19 lung samples, NDP52 rarely colocalizes with galectin-8, unlike healthy lung cells. The 3CL pro substrate degradome establishes a foundational substrate atlas to accelerate exploration of SARS-CoV-2 pathology and drug design.

Hyperbranched polyglycerol is one of the most widely studied biocompatible dendritic polymer and showed promising applications. Here, we summarized the recent advancements in the field.

A family of chiral zinc amido-oxazolinate complexes are shown to be highly active and isoselective initiators for the ring-opening polymerization (ROP) of rac-lactide, yielding isotactic stereoblock polylactides (PLA) with Pm up to 0.91. This represents the highest isoselectivity observed with zinc-based catalysts for ROP of rac-lactide.

The introduction of cell-based therapies has provided new and unique strategies to treat many diseases and disorders including the recent approval of CAR-T cell therapy for the leukemia. Cell surface engineering is a methodology in which the cell surface is tailored to modulate cellular function and interactions. In addition to genetic engineering of cell surface proteins, a wide array of robust, innovative and elegant approaches have been developed to selectively target the cell surface. In this review, we will introduce the leading strategies currently used in cell surface engineering including broadly reactive chemical ligations and physical associations as well as more controlled approaches as demonstrated in genetic, enzymatic and metabolic engineering. Prominent applications of these strategies for cell-based therapies will be highlighted including targeted cell death, control over stem cell fate, immunoevasion, blood transfusion and the delivery of cells to target tissues. Advances will be focused specifically on cells which are the most promising in generating cell-based therapeutics including red blood cells, white blood cells (lymphocytes, macrophages), stem cells (multipotent and pluripotent), islet cells, cancer cells, and endothelial cells.