De novo design of SARS-CoV-2 main protease inhibitors with characteristic binding modes.

The coronavirus disease 2019 (COVID-19) is caused by a novel coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which spreads rapidly all over the world. The main protease (Mpro) is significant to the replication and transcription of viruses, making it an attractive drug target against coronaviruses. Here, we introduce a series of novel inhibitors which are designed de novo through structure-based drug design approach that have great potential to inhibit SARS-CoV-2 Mproin vitro. High-resolution structures show that these inhibitors form covalent bonds with the catalytic cysteine through the novel dibromomethyl ketone (DBMK) as a reactive warhead. At the same time, the designed phenyl group beside the DBMK warhead inserts into the cleft between H41 and C145 through π-π stacking interaction, splitting the catalytic dyad and disrupting proton transfer. This unique binding model provides novel clues for the cysteine protease inhibitor development of SARS-CoV-2 as well as other pathogens.

From Polyester Plastics to Diverse Monomers via Low-Energy Upcycling.

Polyester plastics, constituting over 10% of the total plastic production, are widely used in packaging, fiber, single-use beverage bottles, etc. However, their current depolymerization processes face challenges such as non-broad spectrum recyclability, lack of diversified high-value-added depolymerization products, and crucially high energy consumption. Herein, an efficient strategy is developed for dismantling the compact structure of polyester plastics to achieve diverse monomer recovery. Polyester plastics undergo swelling and decrystallization with a low depolymerization energy barrier via synergistic effects of polyfluorine/hydrogen bonding, which is further demonstrated via density functional theory calculations. The swelling process is elucidated through scanning electron microscopy analysis. Obvious destruction of the crystalline region is demonstrated through X-ray crystal diffractometry curves. PET undergoes different aminolysis efficiently, yielding nine corresponding high-value-added monomers via low-energy upcycling. Furthermore, four types of polyester plastics and five types of blended polyester plastics are closed-loop recycled, affording diverse monomers with exceeding 90% yields. Kilogram-scale depolymerization of real polyethylene terephthalate (PET) waste plastics is successfully achieved with a 96% yield.

Degradation of plastic wastes to commercial chemicals and monomers under visible light.

Plastics are playing an incrementally extensive and irreplaceable role in human life, but with alarming cyclic unsustainability. Numerous attempts have been undertaken to recycle plastics, among which chemical recycling from waste plastics back to chemicals and monomers has attracted great attention. Herein, the depolymerization of nine types of plastics to commercial chemicals and monomers was achieved under ambient conditions via synergetic integrated uranyl-photocatalysis, which contains a process for converting five kinds of mixed plastics into a value-added product. The degradation processes were depicted in terms of variation in scanning electron microscopy imaging, distinction in the X-ray diffraction pattern, alteration in water contact angle, and dynamic in molecular weight distribution. Single electron transfer, hydrogen atom transfer, and oxygen atom transfer were synergistically involved in uranyl-photocatalysis, which were substantiated by mechanistic studies. Relying on flow system design, the chemical recycling of plastics was feasible for kilogram-scale degradation of post-consumer-waste polyethylene terephthalate bottles to commercial chemicals, displaying a promising practical application potential in the future.