Arbidol, ethyl-6-bromo-4-[(dimethylamino)-methyl]-5-hydroxy-1-methyl-2-[(phenylthio)methyl]-in dole-3-carboxylate hydrochloride monohydrate, is an antiviral chemical agent. In this report, we studied the antiviral activity of arbidol against a panel of human respiratory viruses, namely influenza A virus (FLU-A, A/PR/8/34 H1N1), respiratory syncytial virus (RSV), human rhinovirus type 14 (HRV 14), coxsackie virus B3 (CVB3) and adenovirus type 7 (AdV-7) in vitro in cell culture. Arbidol was found to present potent inhibitory activity against enveloped and non-enveloped RNA viruses, including FLU-A, RSV, HRV 14 and CVB3 when added before, during, or after viral infection, with 50% inhibitory concentration (IC50) ranging from 2.7 to 13.8 microg/ml. However, arbidol showed selective antiviral activity against AdV-7, a DNA virus, only when added after infection (therapeutic index (TI) = 5.5). Orally administered arbidol at 50 or 100 mg/kg/day beginning 24 h pre-virus exposure for 6 days significantly reduced mean pulmonary virus yields and the rate of mortality in mice infected with FLU-A (A/PR/8/34 H1N1). Our results suggest that arbidol has the ability to elicit protective broad-spectrum antiviral activity against a number of human pathogenic respiratory viruses.
The 5'-cap structure is a distinct feature of eukaryotic mRNAs and is important for RNA stability and protein translation by providing a molecular signature for the distinction of self or non-self mRNA. Eukaryotic viruses generally modify the 5'-end of their RNAs to mimic the cellular mRNA structure, thereby facilitating viral replication in host cells. However, the molecular organization and biochemical mechanisms of the viral capping apparatus typically differ from its cellular counterpart, which makes viral capping enzymes attractive targets for drug discovery. Our previous work showed that SARS coronavirus (SARS-CoV) non-structural protein 14 represents a structurally novel and unique guanine-N7-methyltransferase (N7-MTase) that is able to functionally complement yeast cellular N7-MTase. In the present study, we developed a yeast-based system for identifying and screening inhibitors against coronavirus N7-MTase using both 96-well and 384-well microtiter plates. The MTase inhibitors previously identified by in vitro biochemical assays were tested, and some, such as sinefungin, effectively suppressed N7-MTase in the yeast system. However, other compounds, such as ATA and AdoHcy, did not exert an inhibitory effect within a cellular context. These results validated the yeast assay system for inhibitor screening yet also demonstrated the difference between cell-based and in vitro biochemical assays. The yeast system was applied to the screening of 3000 natural product extracts, and three were observed to more potently inhibit the activity of coronavirus than human N7-MTase.
Vanadium redox flow batteries (VRFB), originally proposed by Skyllas-Kazacos et al., have been considered as one of the most promising energy storage systems for intermittently renewable energy. However, the poor electrochemical activity and hydrophobicity of graphite felt electrode greatly limit energy storage efficiency of VRFB system. In this paper, two nitrogen-doped (N-doped) graphite felts, obtained by heat-treating in an NH 3 atmosphere at 600°C and 900°C, have been investigated as electrodes with high electrochemical performance for vanadium redox flow batteries. In particular, the one obtained at 900°C exhibits an excellent electrochemical activity for both V 2+ /V 3+ and VO 2+ /VO 2 + redox couples. The cells with different graphite felt electrodes were assembled, and the charge-discharge performance was evaluated. The cell with the N-doped graphite felts has larger discharge capacity, discharge capacity retention, and energy efficiency, especially with the sample treated at 900°C. The average energy efficiency of the cell with the 900°C treated N-doped graphite felts is 86.47%, 5.44% higher than that of the cell with the pristine graphite felt electrodes. These enhanced electrochemical properties of the N-doped graphite felt electrodes are attributed to the increased electrical conductivity, more active sites, and better wettability provided by the introduction of the nitrogenous groups on the surface of graphite felts. It indicates that N-doped graphite felts have promising application prospect in VRFB.
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