Ebola virus (EBOV) is a key member of Filoviridae family and causes severe human infectious diseases with high morbidity and mortality. As a typical negative-sense single-stranded RNA (−ssRNA) viruses, EBOV possess a nucleocapsid protein (NP) to facilitate genomic RNA encapsidation to form viral ribonucleoprotein complex (RNP) together with genome RNA and polymerase, which plays the most essential role in virus proliferation cycle. However, the mechanism of EBOV RNP formation remains unclear. In this work, we solved the high resolution structure of core domain of EBOV NP. The polypeptide of EBOV NP core domain (NPcore) possesses an N-lobe and C-lobe to clamp a RNA binding groove, presenting similarities with the structures of the other reported viral NPs encoded by the members from Mononegavirales order. Most strikingly, a hydrophobic pocket at the surface of the C-lobe is occupied by an α-helix of EBOV NPcore itself, which is highly conserved among filoviridae family. Combined with other biochemical and biophysical evidences, our results provides great potential for understanding the mechanism underlying EBOV RNP formation via the mobility of EBOV NP element and enables the development of antiviral therapies targeting EBOV RNP formation.

A recently reported potent inhibitor of enterovirus 71 3C protease, (R)-1, was found to have stability and potential toxicity issues due to the presence of a cyanohydrin moiety. Modifying the labile cyanohydrin moiety, by serendipity, led to the discovery of 4-iminooxazolidin-2-onebased inhibitors 4e and 4g with potent inhibitory activity and significantly improved stability. In vivo pharmacokinetic studies of 4e also demonstrated high plasma exposure and moderate half-life. These compounds have shown potential of becoming anti-EV71 drug candidates.

Infections caused by Gram-positive and -negative bacteria are one of the foremost causes of morbidity and mortality globally. Antibiotics are the mainstay of therapy for bacterial infections, but the emergence and wide spread of drug-resistant pathogens have already become a huge issue for public healthcare systems. The coumarin moiety, which is ubiquitous in nature, could bind to the B subunit of DNA gyrase in bacteria and inhibit DNA supercoiling by blocking the ATPase activity; hence, coumarin derivatives possess potential antibacterial activity. Several coumarin-containing hybrids such as coumermycin A1, clorobiocin, and novobiocin have already been used in clinical practice for the treatment of various bacterial infections; thus, it is conceivable that hybridization of the coumarin moiety with other antibacterial pharmacophores may provide opportunities for the development of novel antibiotics. This review outlines the advances in coumarin-containing hybrids with antibacterial potential in the recent 5 years and the structure-activity relationships are also discussed. K E Y W O R D S antibacterial, coumarin, hybrid compounds, structure-activity relationships

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