Molecularly imprinted polymeric coatings for sensitive and selective gravimetric detection of artemether

Monitoring antimalarial drugs is necessary for clinical assays, human health, and routine quality control practices in pharmaceutical industries. Herein, we present the development of sensor coatings based on molecularly imprinted polymers (MIPs) combined with quartz crystal microbalance (QCM) for sensitive and selective gravimetric detection of an antimalarial drug: artemether. The MIP coatings are synthesized by using artemether as the template in a poly(methacrylic acid-co-ethylene glycol dimethacrylate) matrix. Artemether-MIP and the non-imprinted polymer (NIP) control or reference layers are deposited on 10 MHz dual-electrode QCM by spin coating (187 ± 9 nm layer thickness after optimization). The coatings are characterized by FTIR spectroscopy and atomic force microscopy that reveal marked differences among the MIP and NIP. The MIP-QCM sensor exhibits high sensitivity (0.51 Hz ppm⁻¹) with sub-10 ppm detection and quantification limits. The MIP-QCM sensor also exhibits a 6-fold higher sensitivity compared to the NIP-QCM, and a dynamic working range of 30–100 ppm. The response time of MIP-QCM devices for a single cycle of analyte adsorption, signal saturation, and MIP regeneration is less than 2.5 min. The sensor also demonstrates selectivity factors of artemether-MIP of 2.2 and 4.1 compared to artemisinin and lumefantrine, respectively. Reversibility tests reveal less than 5% variation in sensor responses over three cycles of measurements at each tested concentration. The MIP-QCM showed lower detection limits than conventional HPLC-UV, and faster response time compared to HPLC-UV and liquid chromatography-mass spectrometry (LC-MS).

Chemical structures of the antimalarial drugs: artemisinin, artemether (a methyl ether derivative of artemisinin), and lumefantrine.     

Ilimaquinone (marine sponge metabolite) as a novel inhibitor of SARS-CoV-2 key target proteins in comparison with suggested COVID-19 drugs: designing,docking and molecular dynamics simulation study

The outbreak of novel coronavirus, SARS-CoV-2, has infected more than 36 million people and caused approximately 1 million deaths around the globe as of 9 October 2020. The escalating outspread of the virus and rapid rise in the number of cases require the instantaneous development of effectual drugs and vaccines. Presently, there are no approved drugs or vaccine available to treat the infection. In such scenario, one of the propitious therapeutic approaches against viral infection is to explore enzyme inhibitors amidst natural compounds, utilizing computational approaches aiming to get products with negligible side effects. In the present study, the inhibitory prospects of ilimaquinone (marine sponge metabolite) were assessed in comparison with hydroxychloroquine, azithromycin, favipiravir, ivermectin and remdesivir at the active binding pockets of nine different vital SARS-CoV-2 target proteins (spike receptor binding domain, RNA-dependent RNA polymerase, Nsp10, Nsp13, Nsp14, Nsp15, Nsp16, main protease, and papain-like-protease), employing an in silico molecular interaction based approach. In addition, molecular dynamics (MD) simulations of the SARS-CoV-2 papain-like protease (PLpro)–ilimaquinone complex were also carried out to calculate various structural parameters including root mean square fluctuation (RMSF), root mean square deviation (RMSD), radius of gyration (R_g) and hydrogen bond interactions. PLpro is a promising drug target, due to its imperative role in viral replication and additional function of stripping ubiquitin and interferon-stimulated gene 15 (ISG15) from host-cell proteins. In light of the possible inhibition of all vital SARS-CoV-2 target proteins, our study has emphasized the importance to study in depth ilimaquinone actions in vivo.

Inhibitory potential of ilimaquinone (marine sponge metabolite) against nine essential SARS-CoV-2 target proteins, employing a molecular interaction and dynamics simulation approach.     

Design and formulation of polymeric nanosponge tablets with enhanced solubility for combination therapy

Three drugs namely caffeine, paracetamol, and aceclofenac are commonly used for treating various acute and chronic pain related ailments. These 3 drugs have varied solubility profiles, and formulating them into a single tablet did not have the desired dissolution profile for drug absorption. The objective of the present research was to tailor the drug release profile by altering drug solubility. This was achieved by loading the drug into nanosponges. Here, three-dimensional colloidal nanosponges were prepared using β-cyclodextrin with dimethyl carbonate as a cross-linker using the hot-melt compression method. The prepared nanosponges were characterized by FTIR, ¹H NMR spectroscopy, DSC, XRPD studies and SEM. The FTIR and DSC results obtained indicated polymer-drug compatibility. The ¹H NMR spectroscopy results obtained indicated the drug entrapment within nanosponges with the formation of the inclusion complex. XRPD studies showed that the loaded drug had changed crystalline properties altering drug solubility. SEM photographs revealed the porous and spongy texture on the surface of the nanosponge. Box–Behnken experimental design was adopted for the optimization of nanosponge synthesis. Among the synthesized nanosponges containing paracetamol, aceclofenac and caffeine, batch F3–P31, F3–A31 and F3–C31 were considered optimized. Their particle size was 185, 181 and 199 nm with an entrapment efficiency of 81.53, 84.96, and 89.28% respectively. These optimized nanosponges were directly compressed into tablets and were studied for both pre and post-compression properties including in vitro drug release. The prepared tablet showed desired drug dissolution properties compared to the pure drug. The above outcomes indicated the applicability of nanosponges in modulating the drug release with varied solubility for combination therapy.

Polymeric nanosponges as potential carriers for successful combination therapy of poorly soluble drugs (paracetamol, aceclofenac, caffeine).     

Prevalence of post-traumatic stress disorder during the COVID-19 pandemic in Saudi Arabia

BackgroundThe coronavirus diseases of 2019 (COVID-19) pandemic was classified as one of the worst pandemics in the 21st century. Its rapid transmission, unpredicted mortality rate, and the uncertainty surrounding its transmission method have evoked additional fear and anxiety. Nonetheless, to the best of our knowledge, no prior study has explored PTSD prevalence three months after the start of the quarantine procedures in Saudi Arabia nor has examined PTSD prevalence by three different methods.ObjectiveThis observational cross-sectional study aimed to identify the prevalence, severity, and influencing factors of PTSD in different regions of Saudi Arabia three months after the onset of the quarantine procedures related to the COVID-19 pandemic.MethodsThrough the month of June 2020, 1374 people (49.05% men and 50.95% women) completed a 35-item, 10-minute online. The prevalence of PTSD was measured using PCL-S (specific for COVID-19) that assesses the 17 symptoms of PTSD. Resilience was measured using 2-items Arabic version of the Connor-Davidson Resilience Scale 2 (CD-RISC 2).ResultsWe calculated the prevalence by three methods, namely, PTSD cut-off score, criteria, and combined, and the prevalence was 22.63%, 24.8%, and 19.6%, respectively. Female participants showed higher prevalence than male. As well, participants who were either tested positive or suspected of having been infected with COVID-19 showed higher PTSD prevalence. Higher resilience was associated with lower PTSD prevalence.ConclusionsThis was the first study to report PTSD prevalence by three differential methods three months after the onset of the quarantine procedures related to the COVID-19 pandemic in Saudi Arabia. We observed a significant impact of the COVID-19 pandemic in the Saudi population; therefore, great attention should be performed in implementing new procedures that deal with the highlighted risk factors, especially in vulnerable groups, to overcome the psychological impact of the COVID-19 pandemic.     

Identification of potential inhibitors of Zika virus NS5 RNA-dependent RNA polymerase through virtual screening and molecular dynamic simulations

Zika virus (ZIKV) is one of the mosquito borne flavivirus with several outbreaks in past few years in tropical and subtropical regions. The non-structural proteins of flaviviruses are suitable active targets for inhibitory drugs due to their role in pathogenicity. In ZIKV, the non-structural protein 5 (NS5) RNA-Dependent RNA polymerase replicates its genome. Here we have performed virtual screening to identify suitable ligands that can potentially halt the ZIKV NS5 RNA dependent RNA polymerase (RdRp). During this process, we searched and screened a library of ligands against ZIKV NS5 RdRp. The selected ligands with significant binding energy and ligand-receptor interactions were further processed. Among the selected docked conformations, top five was further optimized at atomic level using molecular dynamic simulations followed by binding free energy calculations. The interactions of ligands with the target structure of ZIKV RdRp revealed that they form strong bonds within the active sites of the receptor molecule. The efficacy of these drugs against ZIKV can be further analyzed through in-vitro and in-vivo studies.     

B‐Type Natriuretic Peptide Levels Predict Ventricular Arrhythmia Post Left Ventricular Assist Device Implantation

B‐type natriuretic peptide (BNP) levels have been shown to predict ventricular arrhythmia (VA) and sudden death in patients with heart failure. We sought to determine whether BNP levels before left ventricular assist device (LVAD) implantation can predict VA post LVAD implantation in advanced heart failure patients. We conducted a retrospective study consisting of patients who underwent LVAD implantation in our institution during the period of May 2009–March 2013. The study was limited to patients receiving a HeartMate II or HeartWare LVAD. Acute myocardial infarction patients were excluded. We compared between the patients who developed VA within 15 days post LVAD implantation to the patients without VA. A total of 85 patients underwent LVAD implantation during the study period. Eleven patients were excluded (five acute MI, four without BNP measurements, and two discharged earlier than 13 days post LVAD implantation). The incidence of VA was 31%, with 91% ventricular tachycardia (VT) and 9% ventricular fibrillation. BNP remained the single most powerful predictor of VA even after adjustment for other borderline significant factors in a multivariate logistic regression model (P < 0.05). BNP levels are a strong predictor of VA post LVAD implantation, surpassing previously described risk factors such as age and VT in the past.     

Influence of treatment duration with a 600-mg dose of clopidogrel before percutaneous coronary revascularization

OBJECTIVES: We examined clinical outcomes in the Intracoronary Stenting and Antithrombotic Regimen-Rapid Early Action for Coronary Treatment (ISAR-REACT) trial based on the duration of pretreatment with a 600-mg loading dose of clopidogrel. BACKGROUND: The influence of the treatment duration with a 600-mg dose of clopidogrel before percutaneous coronary revascularization on early outcomes remains uncertain. METHODS: Among 2,159 patients with coronary disease who underwent percutaneous coronary intervention (PCI) in the ISAR-REACT trial, we examined clinical outcomes relative to the duration of pretreatment with a 600-mg dose of clopidogrel: (2 to 3 h, 3 to 6 h, 6 to 12 h, or >12 h). Patients were randomly assigned to adjunctive therapy with abciximab or placebo at the beginning of the study. The primary end point was a composite of death, myocardial infarction, or urgent revascularization within 30 days after randomization. RESULTS: No significant differences were observed between patient groups regarding the duration of pretreatment, irrespective of assignment to abciximab or placebo (p = 0.27 for interaction among abciximab/clopidogrel and placebo/clopidogrel treatment at each time interval). Occurrence of major bleeding also did not differ according to time of initial clopidogrel dosing. CONCLUSIONS: For low-to-intermediate risk patients treated with a 600-mg loading dose of clopidogrel before PCI, incremental clinical benefit within the first 30 days from durations of pretreatment >2 to 3 h was not evident.