EpiMed Coronabank Chemical Collection: Compound selection, ADMET analysis, and utilisation in the context of potential SARS-CoV-2 antivirals.

Antiviral drugs are important for the coronavirus disease 2019 (COVID-19) response, as vaccines and antibodies may have reduced efficacy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. Antiviral drugs that have been made available for use, albeit with questionable efficacy, include remdesivir (Veklury®), nirmatrelvir-ritonavir (Paxlovid™), and molnupiravir (Lagevrio®). To expand the options available for COVID-19 and prepare for future pandemics, there is a need to investigate new uses for existing drugs and design novel compounds. To support these efforts, we have created a comprehensive library of 750 molecules that have been sourced from in vitro, in vivo, and in silico studies. It is publicly available at our dedicated website (https://epimedlab.org/crl/). The EpiMed Coronabank Chemical Collection consists of compounds that have been divided into 10 main classes based on antiviral properties, as well as the potential to be used for the management, prevention, or treatment of COVID-19 related complications. A detailed description of each compound is provided, along with the molecular formula, canonical SMILES, and U.S. Food and Drug Administration approval status. The chemical structures have been obtained and are available for download. Moreover, the pharmacokinetic properties of the ligands have been characterised. To demonstrate an application of the EpiMed Coronabank Chemical Collection, molecular docking was used to evaluate the binding characteristics of ligands against SARS-CoV-2 nonstructural and accessory proteins. Overall, our database can be used to aid the drug repositioning process, and for gaining further insight into the molecular mechanisms of action of potential compounds of interest.

Efficacy and safety of oral gonadotropin-releasing hormone antagonists in moderate-to-severe endometriosis-associated pain: a systematic review and network meta-analysis.

PURPOSE: The aim of this NMA is to comprehensively analyze evidence of oral GnRH antagonist in the treatment of moderate-to-severe endometriosis-associated pain. METHODS: Literature searching was performed to select eligible studies published prior to April 2022 in PubMed, Cochrane, Embase and Web of Science. Randomized controlled trials involving patients who suffered from moderate-to-severe endometriosis-associated pain and treated with oral nonpeptide GnRH antagonists or placebo were included. RESULTS: Elagolix 400 mg and ASP1707 15 mg were most efficient in reducing pelvic pain, dysmenorrhea and dyspareunia. Relugolix 40 mg was best in reducing the analgesics use. The rates of any TEAEs and TEAEs-related discontinuation were highest in relugolix 40 mg and elagolix 250 mg, respectively, while rates of hot flush and headache were highest in relugolix 40 mg and elagolix 150 mg. Significantly decreased spinal BMD was observed in elagolix 250 mg. CONCLUSION: Oral GnRH antagonists were effective in endometriosis-associated pain in 12w, and most of the efficiency and safety outcomes were expressed in a dose-dependent manner, but linzagolix 75 mg was an exception.

Age and Five-Year Outcomes After Carotid Artery Stenting in Symptomatic Carotid Stenosis: A Retrospective Cohort Study.

BACKGROUND: Several clinical trials have reported that periprocedural risk of carotid artery stenting (CAS) increase with age. China is experiencing one of the most rapid transitions to an aging society, while the clinical outcomes of CAS in real-world China are still limited. The study aimed to compare the periprocedural and an extending 5-year event rates between younger and older patients treated by CAS to testify the safety of CAS in older patients in China. METHODS: This is a single center, retrospective cohort study. Symptomatic patients who underwent CAS from Nov 2011 to June 2014 were retrospectively included in this study, The population was divided into two age groups: <70 and ≥70. The main primary endpoint was stroke, myocardial infarction or death occurring at 30 days, or ipsilateral stroke over 5-year after stenting. RESULTS: A total of 103 symptomatic patients (<70: 68%; ≥70: 32%) with CAS included in the study. During the 30-day period, the rate of primary outcome was 1.0% with only one stroke in patients younger than 70 years old (P = 1.000). After five years, the rate of primary outcome was low (10.9%, 10/92) despite some of the patients had major stroke or underwent bilateral C1 stenting. There was no significant difference in the 5-year rates of the primary outcome between the young and old groups (12.3% vs 7.4%, P = .718). Kaplan-Meier estimates of the proportion of study participants with a primary endpoint showed that there was no significant age-dependent difference of the stroke and death outcome in symptomatic patients. CONCLUSIONS: Age (<70 vs ≥ 70) had no influence on the risk of stroke or death in symptomatic patients either in the short or long term. CAS is an optimal treatment for older patients with cervical carotid artery stenosis, and CAS was safe for those with major stroke or bilateral C1 stenting.

Indirect electrochemical reduction of nitrate in water using zero-valent titanium anode: Factors, kinetics, and mechanism.

In this study, indirect electrochemical reduction with zero-valent titanium (ZVT) as anode successfully achieved the selective nitrate removal from simulated groundwater. The maximum nitrate removal efficiency and N2 selectivity reached to 83.4% and 78.5% after 12 h, respectively. Experimental results demonstrated that the gaseous by-products (NO and N2O) were negligible and the nitrate reduction process could be well depicted by pseudo-first-order kinetic model. Decreasing the pH value of electrolyte was favorable to electrical energy utilization efficiency and nitrate removal. The chloride ultimately showed inhibitory effects on electrochemical reduction of nitrate. During the electrochemical reaction, the ZVT lost electrons to generate the reducing agents (Ti3+ and Ti2+), which could afford electrons for nitrate reduction and form the solid by-products TiO2.4Cl0.2N0.1. A 2-stage strategy, indirect electrochemical reduction + hypochlorite treatment (pre-reduction + post-oxidation), was developed to completely remove nitrate and the long-term performance of nitrate reduction was comprehensively evaluated. The effluent nitrate steadily kept at 8.8 mg N/L during 120 h continuous operation when the influent nitrate concentration was 25.9 mg N/L. Simultaneously, nitrite concentration was lower than 0.01 mg N/L, and ammonium and Ti ions were not detected in the effluent.

Heterogeneous activation of peroxymonosulfate using Mn-Fe layered double hydroxide: Performance and mechanism for organic pollutant degradation.

On account of high oxidation ability of sulfate radical-based advanced oxidation processes (AOPs), the eco-friendly catalysts for peroxymonosulfate (PMS) activation have received considerable attentions. Previous studies mainly focused on Cobalt-based catalyst due to its high activation efficiency, such as Co3O4/MnO2 and FeCo-layered double hydroxide (LDH), whereas Cobalt-based catalyst usually has serious risk to environment. To avoid this risk, MnFe-LDH was primarily synthesized in this research by simple co-precipitation and subsequently utilized as an effective catalyst for peroxymonosulfate (PMS) activation to degrade organic pollutants. The experimental results demonstrated that MnFe-LDH with a lower dosage (0.20 g/L) could efficiently activate PMS to achieve 97.56% removal of target organic pollutants Acid Orange 7 (AO7). The AO7 degradation process followed the pseudo-first-order kinetic well with an activation energy of 21.32 kJ/mol. The intrinsic influencing mechanism was also investigated. The quenching experiment and electron spin resonance (ESR) indicated that sulfate and hydroxyl radicals were produced by the effective activation of PMS by MnFe-LDH, resulting in a high rate of decolorization. The possible AO7 removal pathway in the constructed MnFe-LDH/PMS system was presented on the basis of UV-vis spectrum analysis and GC-MS, which suggested that the AO7 degradation was firstly initiated by breaking azo linkages, then generated phenyl and naphthalene intermediates and finally presented as ring-opening products. This effective MnFe-LDH/PMS system showed great application potential in the purification of wastewater contaminated by refractory organic pollutants.

Sulfate radical induced degradation of Methyl Violet azo dye with CuFe layered doubled hydroxide as heterogeneous photoactivator of persulfate.

Persulfate (PS)-based advanced oxidation processes have aroused considerable attentions due to their higher efficiency and wider adaptability to the degradation of bio-recalcitrant organic contaminants. In this study, Cu-Fe layered doubled hydroxide (CuFe-LDH) was employed to degrade Methyl Violet (MV) through heterogeneous photo-activation of PS under visible-light irradiation. The reaction kinetics, degradation mechanism, catalyst stability were investigated in detail. Under the conditions of CuFe-LDH (3:1) dosage 0.2 g/L, PS concentration 0.2 g/L and without initial pH adjustment, 20 mg/L MV was almost completely degraded within 18 min. Electron Spin Resonance (ESR) test and radical quenching experiment indicated that sulfate radicals (SO4-) were the dominant reactive oxidants for the MV decolorization, while hydroxyl radicals (OH) were also involved. The CuFe-LDH/PS/Vis system was applicable at wide range of pH level (3-9). However, extreme pH level would lead to the reduction or transformation of SO4-. The catalyst CuFe-LDH exhibited excellent stability and maintained relatively high catalytic activity to PS even after four recycles. Mechanism study revealed that the redox cycle of Fe3+/Fe2+ and Cu2+/Cu3+ assisted by visible-light irradiation accounted for the enhanced generation of radicals in CuFe-LDH/PS/Vis system, resulting in the improved degradation of organic contaminants. Overall, the CuFe-LDH/PS/Vis process could be a promising approach for the removal of refractory organic pollutants in wastewater.