Background: Secreted antibacterial substances of fungi provide a rich source for new antibiotics. Results: Copsin is a novel fungal antimicrobial peptide that binds in a unique manner to the cell wall precursor lipid II. Conclusion: As part of the defense strategy of a mushroom, copsin kills bacteria by inhibiting the cell wall synthesis. Significance: Copsin provides a novel highly stabilized scaffold for antibiotics.

Dengue fever is a severe, widespread, and neglected disease with more than 2 million diagnosed infections per year. The dengue virus NS2B/NS3 protease (PR) represents a prime target for rational drug design. At the moment, there are no clinical PR inhibitors (PIs) available. We have identified diaryl (thio)ethers as candidates for a novel class of PIs. Here, we report the selective and noncompetitive inhibition of the serotype 2 and 3 dengue virus PR in vitro and in cells by benzothiazole derivatives exhibiting 50% inhibitory concentrations (IC 50 s) in the low-micromolar range. Inhibition of replication of DENV serotypes 1 to 3 was specific, since all substances influenced neither hepatitis C virus (HCV) nor HIV-1 replication. Molecular docking suggests binding at a specific allosteric binding site. In addition to the in vitro assays, a cell-based PR assay was developed to test these substances in a replication-independent way. The new compounds inhibited the DENV PR with IC 50 s in the low-micromolar or submicromolar range in cells. Furthermore, these novel PIs inhibit viral replication at submicromolar concentrations. Dengue viruses (DENVs) are enveloped positive-strand RNA viruses and belong to the family Flaviviridae. DENV is the most important arthropod-borne viral infection. Over one-third of the world population lives in areas of DENV endemicity, and an estimated 390 million infections occur every year. In addition, the number of countries having experienced DENV epidemics has risen from 9 in 1970 to more than 100 today (1, 2). Furthermore, the number of diagnosed infections across America, Southeast Asia, and the Western Pacific nearly doubled from 1.2 million in 2008 to over 2.3 million in 2010 (2). Four different DENV serotypes have been identified so far. Recently, evidence for an additional subtype has been presented (3). Serotypes 1 to 4 are now prevalent in Asia, Africa, and America, and the regions where dengue is endemic are still increasing (4-6), with dengue endangering even Europe and the United States due to vector spread. DENV infections can be associated with dengue fever, but up to 88% of the infections remain inapparent (7). These nonpersistent infected patients serve besides persistently infected mosquitoes as a virus reservoir. Severe DENV infections and especially reinfections may lead to dengue hemorrhagic fever and dengue shock syndrome, with lethality up to 5% (2,8,9). There is neither a vaccination nor a specific treatment for DENV infections.The DENV genome contains a single open reading frame, which encodes the structural proteins capsid, membrane precursor (prM), and envelope and the nonstructural proteins NS1, NS2, NS3, NS4, and NS5 (10). Cellular proteases and the viral serine protease (PR) are responsible for cleaving the viral precursor polyprotein into functional proteins. The DENV PR consists of the amino-terminal domain of the NS3 protein and requires NS2B, a 14-kDa protein, as a cofactor to form a stable complex. This heterodimeric PR cleaves at the capsid-prM, NS2A/NS2...

The first deprotonation of a borohydride anion was achieved by treatment of [BH(CN) ] with strong non-nucleophilic bases, which resulted in the formation of alkali-metal salts of the tricyanoborate dianion B(CN) in up to 97 % yield and 99.5 % purity. [BH(CN) ] is less acidic than (Me Si) NH but a stronger acid than iPr NH. Less sterically hindered, more nucleophilic bases such as PhLi and MeLi mostly attack a CN group under formation of imine dianions [RC(N)B(CN) ] , which can be hydrolyzed to ketones of the [RC(O)B(CN) ] type. The boron-centered nucleophile B(CN) reacts with CO and CN reagents to give salts of the [B(CN) CO ] dianion and the tetracyanoborate anion [B(CN) ] , respectively, in excellent yields.

Die Reaktionen von [BH(CN) 3 ] À mit starken nichtnucleophilen Basen sind die ersten Beispiele fürd ie Deprotonierung eines Hydridoborat-Anions.D iese liefern Alkalimetall-Salzem it dem Tricyanoborat-Dianion B(CN) 3 2À in bis zu 97 %A usbeute und 99.5 %R einheit. [BH(CN) 3 ] À ist weniger acide als (Me 3 Si) 2 NH, aber eine stärkere Säure als iPr 2 NH. Sterischw eniger gehinderte,s t ärker nucleophile Basen wie PhLi und MeLi greifen hauptsächlichd ie CN-Gruppen unter Bildung von Imino-Dianionen [RC(N)B(CN) 3 ] 2À an, die mit Wasser zu Ketonen vom Typ[RC(O)B(CN) 3 ] À reagieren. Das Bor-zentrierte Nucleophil B(CN) 3 2À reagiert mit CO 2 und CN + -Reagenzien in exzellenten Ausbeuten zu Salzen mit dem [B(CN) 3 CO 2 ] 2À -b zw.d em Tetracyanoborat-Anion [B-(CN) 4 ] À .

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