We developed a de novo protein design strategy to swiftly engineer decoys for neutralizing pathogens that exploit extracellular host proteins to infect the cell. Our pipeline allowed the design, validation, and optimization of de novo hACE2 decoys to neutralize SARS-CoV-2. The best decoy, CTC-445.2, binds with low nanomolar affinity and high specificity to the RBD of the spike protein. Cryo-EM shows that the design is accurate and can simultaneously bind to all three RBDs of a single spike protein. Because the decoy replicates the spike protein target interface in hACE2, it is intrinsically resilient to viral mutational escape. A bivalent decoy, CTC-445.2d, shows ~10-fold improvement in binding. CTC-445.2d potently neutralizes SARS-CoV-2 infection of cells in vitro and a single intranasal prophylactic dose of decoy protected Syrian hamsters from a subsequent lethal SARS-CoV-2 challenge.

We report the unambiguous assignments of the (1)H and (13)C NMR spectra of one new natural product, namely, 6,8-di-O-methyl versiconol (1) together with one known anthraquinone aversin (2) and two xanthones 5-methoxysterigmatocystin (3) and sterigmatocystin (4). These compounds were all isolated from the mangrove endophytic fungus ZSUH-36 from the South China Sea. 1D and 2D NMR experiments including COSY, HMQC and HMBC were used to elucidate the structures. Variations in the (1)H NMR spectrum of 6,8-di-O-methyl versiconol (1) were also observed in the temperature range 25-75 degrees C. In addition, the plausible biogenetic path from 1 to 2 is discussed.

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Efforts to induce angiogenesis have been dedicated to developing novel strategies to fabricate an ideal scaffold for bone tissue engineering. In order to mimic the environment of the repair process in vivo, this study was performed to investigate the effect of strontium-doped calcium polyphosphate (SCPP) on angiogenesis-related behaviors of umbilical vein endothelial cells and osteoblasts co-cultured in vitro.The results indicate that, compared with those in calcium polyphosphate (CPP) and hydroxyapatite (HA) group, cells attached and spread better with a significantly improved cell proliferation in SCPP group.More importantly, in vitro co-culture demonstrated a significant improvement in the VEGF and bFGF expression levels in SCPP groups. The results also demonstrated that SCPP could effectively enhance VEGF and bFGF expression from host cell in vivo and thereby inducing angiogenesis in implanted scaffolds. SCPP could be used as a potential material with stimulating angiogenesis, which would provide a novel thought for resolving the problem of angiogenesis in bone tissue engineering.