•We reviewed the discovery and development process of broad-spectrum antiviral agents.•We summarized the information on 120 safe-in-man agents in a freely accessible database.•Further studies will ...increase the number of broad-spectrum antivirals, expand the spectrum of their indications, and identify drug combinations for treatment of emerging and re-emerging viral infections.
Viral diseases are one of the leading causes of morbidity and mortality in the world. Virus-specific vaccines and antiviral drugs are the most powerful tools to combat viral diseases. However, broad-spectrum antiviral agents (BSAAs, i.e. compounds targeting viruses belonging to two or more viral families) could provide additional protection of the general population from emerging and re-emerging viral diseases, reinforcing the arsenal of available antiviral options. Here, we review discovery and development of BSAAs and summarize the information on 120 safe-in-man agents in a freely accessible database (https://drugvirus.info/). Future and ongoing pre-clinical and clinical studies will increase the number of BSAAs, expand the spectrum of their indications, and identify drug combinations for treatment of emerging and re-emerging viral infections as well as co-infections.
Viruses are the major causes of acute and chronic infectious diseases in the world. According to the World Health Organization, there is an urgent need for better control of viral diseases. ...Repurposing existing antiviral agents from one viral disease to another could play a pivotal role in this process. Here, we identified novel activities of obatoclax and emetine against herpes simplex virus type 2 (HSV-2), echovirus 1 (EV1), human metapneumovirus (HMPV) and Rift Valley fever virus (RVFV) in cell cultures. Moreover, we demonstrated novel activities of emetine against influenza A virus (FLUAV), niclosamide against HSV-2, brequinar against human immunodeficiency virus 1 (HIV-1), and homoharringtonine against EV1. Our findings may expand the spectrum of indications of these safe-in-man agents and reinforce the arsenal of available antiviral therapeutics pending the results of further in vitro and in vivo tests.
•Broad-spectrum antivirals target ≥3 viral diseases.•108 safe-in-man broad-spectrum antiviral agents were identified.•These agents could reinforce the arsenal of available antiviral therapeutics.
...Broad-spectrum antivirals (BSAs) are agents that inhibit replication of several human viruses. Here, we review 108 approved, investigational, and experimental BSAs, for which safety profiles in humans are available. The most effective and tolerable BSAs could reinforce the arsenal of available antiviral therapeutics pending the results of further pre-clinical and clinical studies.
Viruses are one of the major causes of acute and chronic infectious diseases and thus a major contributor to the global burden of disease. Several studies have shown how viruses have evolved to ...hijack basic cellular pathways and evade innate immune response by modulating key host factors and signaling pathways. A collective view of these multiple studies could advance our understanding of virus-host interactions and provide new therapeutic perspectives for the treatment of viral diseases. Here, we performed an integrative meta-analysis to elucidate the 17 different host-virus interactomes. Network and bioinformatics analyses showed how viruses with small genomes efficiently achieve the maximal effect by targeting multifunctional and highly connected host proteins with a high occurrence of disordered regions. We also identified the core cellular process subnetworks that are targeted by all the viruses. Integration with functional RNA interference (RNAi) datasets showed that a large proportion of the targets are required for viral replication. Furthermore, we performed an interactome-informed drug re-purposing screen and identified novel activities for broad-spectrum antiviral agents against hepatitis C virus and human metapneumovirus. Altogether, these orthogonal datasets could serve as a platform for hypothesis generation and follow-up studies to broaden our understanding of the viral evasion landscape.
Raman spectroscopy is a viable tool within process analytical technologies due to recent technological advances. In this article, we evaluate the feasibility of Raman spectroscopy for in-line ...applications in the food industry by estimating the concentration of the fatty acids EPA + DHA in ground salmon samples (n = 63) and residual bone concentration in samples of mechanically recovered ground chicken (n = 66). The samples were measured under industry like conditions: They moved on a conveyor belt through a dark cabinet where they were scanned with a wide area illumination standoff Raman probe. Such a setup should be able to handle relevant industrial conveyor belt speeds, and it was studied how different speeds (i.e., exposure times) influenced the signal-to-noise ratio (SNR) of the Raman spectra as well as the corresponding model performance. For all samples we applied speeds that resulted in 1 s, 2 s, 4 s, and 10 s exposure times. Samples were scanned in both heterogenous and homogenous state. The slowest speed (10 s exposure) yielded prediction errors (RMSECV) of 0.41%EPA + DHA and 0.59% ash for the salmon and chicken data sets, respectively. The more in-line relevant exposure time of 1 s resulted in increased RMSECV values, 0.84% EPA + DHA and 0.84% ash, respectively. The increase in prediction error correlated closely with the decrease in SNR. Further improvements of model performance were possible through different noise reduction strategies. Model performance for homogenous and heterogenous samples was similar, suggesting that the presented Raman scanning approach has the potential to work well also on intact heterogenous foods. The estimation errors obtained at these high speeds are likely acceptable for industrial use, but successful strategies to increase SNR will be key for widespread in-line use in the food industry.
In this work, silicon/carbon composites for anode electrodes of Li-ion batteries are prepared from Elkem's Silgrain® line. Gentle ball milling is used to reduce particle size of Silgrain, and the ...resulting Si powder consists of micrometic Si with some impurities. Silicon/carbon composite with CMC/SBR as a dual binder can achieve more than 1200 cycles with a capacity of 1000 mAh g
of Si. This excellent electrochemical performance can be attributed to the use of a buffer as a solvent to control the pH of the electrode slurry, and hence the bonding properties of the binder to the silicon particles. In addition, the use of FEC as an electrolyte additive is greatly contributing to a stabilized cycling by creating a more robust SEI layer. This work clearly demonstrates the potential of industrial battery grade silicon from Elkem.
Autonomous field robots are being developed for picking of fruit, where each fruit needs to be individually graded and handled. There is therefore a need for rapid and non-destructive sensing to ...measure critical fruit quality parameters. In this article we report how total soluble solids (TSS), a measure for total sugar content, can be measured in strawberries in the field by non-contact near-infrared (NIR) interaction spectroscopy. A specially designed prototype system working in the wavelength range 760-1080 nm was tested for this purpose. This novel instrument was compared with a commercial handheld NIR reflection instrument working in the range 900-1600 nm. The instruments were calibrated in the lab using data collected from 200 strawberries of two varieties and tested in a strawberry field on 50 berries in 2022 and 100 berries in 2023. Both systems performed well during calibration with root mean square errors of cross validation for TSS around 0.49 % and 0.57 %, for interaction and reflection, respectively. For prediction of TSS in new berries in 2023, the interaction system was superior, with a prediction error of 1.0 % versus 8.1 % for the reflection system, most likely because interaction probes deeper into the berries. The results suggest that interaction measurements of average TSS are more robust and would most likely require less calibration maintenance compared to reflection measurements. The non-contact feature is important since it reduces the spread of diseases and physical damage to the berries.
PurposeCoeliac disease (CD) is a common disorder and affects about 1% of the population worldwide. CD in the Trøndelag Health Study (HUNT) is a population-based cohort study which was established to ...provide new knowledge about CD that can improve the diagnostics and management, prevent the onset or progression and expand the knowledge about the role of genetics of the disease.ParticipantsThe cohort is based on the fourth wave of the population-based HUNT study (HUNT4), Norway, performed during 2017–2019, also including linkage to hospital records and the Norwegian Patient Registry (NPR). A total of 54 541 HUNT4 participants with available sera were screened for CD by serology. All seropositive participants were invited to a clinical assessment, including endoscopy with duodenal biopsies, during 2019–2023.Findings to dateA total of 1107 HUNT4 participants (2%) were seropositive for CD and 1048 were eligible for clinical assessment, including biopsy. Of these, 724 participants attended the clinical assessment and 482 were identified with CD. In addition, 371 participants with CD were identified through the hospital records and NPR. In total, 853 participants in HUNT4 with biopsy-verified CD diagnosis were identified.Future plansAll participants in the study will be invited to a follow-up assessment after at least 1 year, including repeated standard serological testing, endoscopy and tissue sampling. The collected data and material will be used to establish the true population-based prevalence of CD. The consequences of CD, including symptoms, deficiencies and comorbidity, will be investigated and possible triggers and predictors, will be studied. With access to serum samples from the previous HUNT surveys in HUNT Biobank, serological signs of CD in prediagnostic samples of seropositive individuals will be used. Genetic studies will identify new CD markers, assess genotype–phenotype links and explore gene–environment correlations.Registrationclinicaltrials.gov identifier: NCT04041622.
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