The CCR5 chemokine receptor acts as a co-receptor for HIV-1 viral entry. Here we report the 2.7 Å resolution crystal structure of human CCR5 bound to the marketed HIV drug Maraviroc. The structure reveals a ligand binding site that is distinct from the proposed major recognition sites for chemokines and the viral glycoprotein gp120, providing insights into the mechanism of allosteric inhibition of chemokine signaling and viral entry. A comparison between CCR5 and CXCR4 crystal structures, along with models of co-receptor/gp120-V3 complexes, suggests that different charge distributions and steric hindrances caused by residue substitutions may be major determinants of HIV-1 co-receptor selectivity. These high-resolution insights into CCR5 can enable structure-based drug discovery for the treatment of HIV-1 infection.

Avoiding wound infection and retaining an appropriate level of moisture around woundz are major challenges in wound care management. Therefore, designing hydrogels with desired antibacterial performance and good water‐maintaining ability is of particular significance to promote the development of wound dressing. Thus a series of hydrogels are prepared by crosslinking of Ag/graphene composites with acrylic acid and N,N′‐methylene bisacrylamide at different mass ratios. The antibacterial performance and accelerated wound‐healing ability of hydrogel are systematically evaluated with the aim of attaining a novel and effective wound dressing. The as‐prepared hydrogel with the optimal Ag to graphene mass ratio of 5:1 (Ag5G1) exhibits stronger antibacterial abilities than other hydrogels. Meanwhile, Ag5G1 hydrogel exhibits excellent biocompatibility, high swelling ratio, and good extensibility. More importantly, in vivo experiments indicate that Ag5G1 hydrogel can significantly accelerate the healing rate of artificial wounds in rats, and histological examination reveals that it helps to successfully reconstruct intact and thickened epidermis during 15 day of healing of impaired wounds. In one word, the present approach can shed new light on designing of antibacterial material like Ag/graphene composite hydrogel with promising applications in wound dressing.

In response to adenosine 5′-diphosphate, the P2Y1 receptor (P2Y1R) facilitates platelet aggregation, and thus serves as an important antithrombotic drug target. Here we report the crystal structures of the human P2Y1R in complex with a nucleotide antagonist MRS2500 at 2.7Å resolution, and with a non-nucleotide antagonist BPTU at 2.2Å resolution. The structures reveal two distinct ligand binding sites, providing atomic details of P2Y1R’s unique ligand binding modes. MRS2500 recognizes a binding site within the seven transmembrane bundle of P2Y1R, which, however, is different in shape and location from the nucleotide binding site in previously determined P2Y12R structure. BPTU binds to an allosteric pocket on the external receptor interface with the lipid bilayer, making it the first structurally characterized selective G protein-coupled receptor (GPCR) ligand located entirely outside of the helical bundle. These high-resolution insights into P2Y1R should enable discovery of new orthosteric and allosteric antithrombotic drugs with reduced adverse effects.