RESUMEN
The exceptional impact of the COVID-19 pandemic has stimulated an intense search for antiviral molecules. Host-targeted antiviral molecules have the potential of presenting broad-spectrum antiviral activity and are also considered as less likely to select for resistant viruses. In this study, we investigated the antiviral activity exerted by AM-001, a specific pharmacological inhibitor of EPAC1, a host exchange protein directly activated by cyclic AMP (cAMP). The cAMP-sensitive protein, EPAC1 regulates various physiological and pathological processes but its role in SARS-CoV-2 and influenza A virus infection has not yet been studied. Here, we provide evidence that the EPAC1 specific inhibitor AM-001 exerts potent antiviral activity against SARS-CoV-2 in the human lung Calu-3 cell line and the African green monkey Vero cell line. We observed a concentration-dependent inhibition of SARS-CoV-2 infectious viral particles and viral RNA release in the supernatants of AM-001 treated cells that was not associated with a significant impact on cellular viability. Furthermore, we identified AM-001 as an inhibitor of influenza A virus in Calu-3 cells. Altogether these results identify EPAC1 inhibition as a promising therapeutic target against viral infections.
Asunto(s)
COVID-19 , Virus de la Influenza A , Gripe Humana , Humanos , Antivirales/farmacología , Chlorocebus aethiops , Gripe Humana/tratamiento farmacológico , Pandemias , ARN Viral , SARS-CoV-2 , Replicación ViralRESUMEN
dc-magnetization data measured down to 40 mK speak against conventional freezing and reinstate YbMgGaO_{4} as a triangular spin-liquid candidate. Magnetic susceptibility measured parallel and perpendicular to the c axis reaches constant values below 0.1 and 0.2 K, respectively, thus indicating the presence of gapless low-energy spin excitations. We elucidate their nature in the triple-axis inelastic neutron scattering experiment that pinpoints the low-energy (E≤J_{0}â¼0.2 meV) part of the excitation continuum present at low temperatures (T
RESUMEN
The first experimental characterization of a multiple energy analysis wide angle backend for a cold triple-axis spectrometer is reported. The multi-analyzer module MultiFLEXX employs 155 detection channels which simultaneously probe an extensive range in wavevector and energy transfer. Successful mapping of magnetic excitations in MnF2 and Ho demonstrate order of magnitude gains in data collection efficiency using this novel type backend. MultiFLEXX is competitive to standard triple-axis spectroscopy in terms of energy resolution and signal-to-noise ratio. A minority of the detector channels is affected by spurious signals inherent to this multiplexing concept. The characteristic signature of these spurious signals easily allows for their discrimination. The instrument concept focuses on detection efficiency in the horizontal scattering plane which makes it an ideal technique for fast mapping and parametric studies including extreme sample environment.