Hydrogen fuel is considered as the cleanest renewable resource and the primary alternative to fossil fuels for future energy supply. Sustainable hydrogen generation is the major prerequisite to realize future hydrogen economy. The electrocatalytic hydrogen evolution reaction (HER), as the vital step of water electrolysis to H 2 production, has been the subject of extensive study over the past decades. In this comprehensive review, we first summarize the fundamentals of HER and review the recent state-of-the-art advances in the low-cost and high-performance catalysts based on noble and non-noble metals, as well as metal-free HER electrocatalysts. We systemically discuss the insights into the relationship among the catalytic activity, morphology, structure, composition, and synthetic method. Strategies for developing an effective catalyst, including increasing the intrinsic activity of active sites and/or increasing the number of active sites, are summarized and highlighted. Finally, the challenges, perspectives, and research directions of HER electrocatalysis are featured.

G-quadruplexes are special secondary structures adopted in some guanine-rich DNA sequences. As guanine-rich sequences are present in important regions of the eukaryotic genome, such as telomeres and the regulatory regions of many genes, such structures may play important roles in the regulation of biological events in the body. G-quadruplexes have become valid targets for new anticancer drugs in the past few decades. Many leading compounds that target these structures have been reported, and a few of them have entered preclinical or clinical trials. Nonetheless, the selectivity of this kind of antitumor compound has yet to be improved in order to suppress the side effects caused by nonselective binding. As drug design targets, the topology and structural characteristics of quadruplexes, their possible biological roles, and the modes and sites of small-ligand binding to these structures should be understood clearly. Herein we provide a summary of published research that has set out to address the above problem to provide useful information on the design of small ligands that target G-quadruplexes. This review also covers research methodologies that have been developed to study the binding of ligands to G-quadruplexes.

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Stabilization of G-quadruplex structures in the promoter region of certain oncogenes is an emerging field in anticancer drug design. Human c-myc gene is one of these oncogenes, and G-quadruplexes have been proven to be the transcriptional controller of this gene. In the present study, the interaction of quindoline derivatives with G-quadruplexes in c-myc was investigated. The experimental results indicated that these derivatives have the ability to induce/stabilize the G-quadruplexes in c-myc, which lead to down-regulation of the c-myc in the Hep G2 cell line. It was found that derivatives with terminal amino groups in their side chains would selectively bind to the isomers with the double nucleotide loops in the absence of K+. Molecular modeling studies revealed the binding mode between the derivatives and the G-quadruplexes is end-stacking at the 3'-position, and the positively charged side chain on the quindoline derivatives may contribute to the selectivity to certain loop isomers of topological quadruplexes as well as the improved stabilization action.

We prepared the three-dimensional model of the SARS-CoV-2 (aka 2019-nCoV) 3C-like protease (3CL ) using the crystal structure of the highly similar (96% identity) ortholog from the SARS-CoV. All residues involved in the catalysis, substrate binding and dimerisation are 100% conserved. Comparison of the polyprotein PP1AB sequences showed 86% identity. The 3C-like cleavage sites on the coronaviral polyproteins are highly conserved. Based on the near-identical substrate specificities and high sequence identities, we are of the opinion that some of the previous progress of specific inhibitors development for the SARS-CoV enzyme can be conferred on its SARS-CoV-2 counterpart. With the 3CL molecular model, we performed virtual screening for purchasable drugs and proposed 16 candidates for consideration. Among these, the antivirals ledipasvir or velpatasvir are particularly attractive as therapeutics to combat the new coronavirus with minimal side effects, commonly fatigue and headache. The drugs Epclusa (velpatasvir/sofosbuvir) and Harvoni (ledipasvir/sofosbuvir) could be very effective owing to their dual inhibitory actions on two viral enzymes. pro 1. Chan JF, Yuan S, Kok KH, et al.: A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. Lancet. 2020; 395(10223): 514-523.PubMed Abstract | Publisher Full Text 2. Muramatsu T, Takemoto C, Kim YT, et al.: SARS-CoV 3CL protease cleaves its C-terminal autoprocessing site by novel subsite cooperativity. Proc Natl Acad Sci U S A. 2016; 113(46): 12997-13002. PubMed Abstract | Publisher Full Text | Free Full Text 3. Krivov GG, Shapovalov MV, Dunbrack RL Jr: Improved prediction of protein sidechain conformations with SCWRL4. Proteins. 2009; 77(4): 778-795. PubMed Abstract | Publisher Full Text | Free Full Text 4. Labbé CM, Rey J, Lagorce D, et al.: MTiOpenScreen: a web server for structurebased virtual screening. Nucleic Acids Res. 2015; 43(W1): W448-W454. PubMed Abstract | Publisher Full Text | Free Full Text 5. Trott O, Olson AJ: AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem. 2010; 31(2): 455-461. PubMed Abstract | Publisher Full Text | Free Full Text 6. Huang C, Wei P, Fan K, et al.: 3C-like proteinase from SARS coronavirus catalyzes substrate hydrolysis by a general base mechanism. Biochemistry. 2004; 43(15): 4568-4574. PubMed Abstract | Publisher Full Text 7. Hsu MF, Kuo CJ, Chang KT, et al.: Mechanism of the maturation process of SARS-CoV 3CL protease. J Biol Chem. 2005; 280(35): 31257-31266. PubMed Abstract | Publisher Full Text 8. Barrila J, Bacha U, Freire E: Long-range cooperative interactions modulate dimerization in SARS 3CL pro . Biochemistry. 2006; 45(50): 14908-14916. PubMed Abstract | Publisher Full Text | Free Full Text 9. Barrila J, Gabelli SB, Bacha U, et al.: Mutation of Asn28 disrupts the dimerization and enzymatic activity of SARS 3CL pro . Biochemistry. 2010; 49(20): ...