Mechanism of Inhibition of Enveloped Virus Membrane Fusion by the Antiviral Drug Arbidol

The broad-spectrum antiviral arbidol (Arb) inhibits cell entry of enveloped viruses by blocking viral fusion with host cell membrane. To better understand Arb mechanism of action, we investigated its interactions with phospholipids and membrane peptides. We demonstrate that Arb associates with phospholipids in the micromolar range. NMR reveals that Arb interacts with the polar head-group of phospholipid at the membrane interface. Fluorescence studies of interactions between Arb and either tryptophan derivatives or membrane peptides reconstituted into liposomes show that Arb interacts with tryptophan in the micromolar range. Interestingly, apparent binding affinities between lipids and tryptophan residues are comparable with those of Arb IC50 of the hepatitis C virus (HCV) membrane fusion. Since tryptophan residues of membrane proteins are known to bind preferentially at the membrane interface, these data suggest that Arb could increase the strength of virus glycoprotein's interactions with the membrane, due to a dual binding mode involving aromatic residues and phospholipids. The resulting complexation would inhibit the expected viral glycoprotein conformational changes required during the fusion process. Our findings pave the way towards the design of new drugs exhibiting Arb-like interfacial membrane binding properties to inhibit early steps of virus entry, i.e., attractive targets to combat viral infection

The start of X-ray generator NESTOR comissioning

The first results of the NESTOR facility commissioning are presented. 60 MeV electron linac injector has been tested and the first electron beam with project parameters was registered at the screen monitors. Electron beam was passed through the transportation channel and injection system. The beamh of electrons was observed and controlled in the screen monitors in the expected range.Перші результати вводу в експлуатацію генератора НЕСТОР представлені. Інжектор-лінійний прискорювач на 60 МеВ електронів був випробуван, та перший пучок із проектними параметрами було зареєстровано на екранах моніторів. Електронний пучок проведено крізь канал транспортування та системи вводу в вакуумну камеру накопичувача. Пучок електронів спостерігається і контролюється на екранах моніторів в очікуваному діапазоні.Представлены первые результаты ввода в эксплуатацию генератора НЕСТОР. Инжектор-линейный ускоритель на 60 МэВ электронов был испытан, и первый пучок с проектными параметрами был зарегистрирован на экранах мониторов. Электронный пучок проведен через канал транспортировки и системы ввода в вакуумную камеру накопителя. Пучок электронов наблюдается и контролируется на экране мониторов в ожидаемом диапазоне

Chikungunya virus: emerging targets and new opportunities for medicinal chemistry

Chikungunya virus is an emerging arbovirus that is widespread in tropical regions and is spreading quickly to temperate climates with recent epidemics in Africa and Asia and documented outbreaks in Europe and the Americas. It is having an increasingly major impact on humankind, with potentially life-threatening and debilitating arthritis. There is no treatment available, and only in the past 24 months have lead compounds for development as potential therapeutics been reported. This Perspective discusses the chikungunya virus as a significant, new emerging topic for medicinal chemistry, highlighting the key viral target proteins and their molecular functions that can be used in drug design, as well as the most important ongoing developments for anti-chikungunya virus research. It represents a complete picture of the current medicinal chemistry of chikungunya, supporting the development of chemotherapeutics through drug discovery and design targeting this virus