Spirulina platensis from Nomayos: a potential health food for the management of COVID-19 infection

The proteins (37%), carbohydrates (24.4%) and lipids (30.1%) contents of S. platensis from Nomayos provide the body with its structural and energy needs for about 518.8 Kcal per 100g of spirulina. Polyphenols (56.4 mEq. QE / g ES.), flavanols (13.2 mEq. QE / g ES.) flavonoids (21.2 mEq. QE / g ES.), carotenoids (3, 8%) and phycocyanin (16.15%) is responsible of its antioxidant capacities (7.5 + 0.33 mg eq. Vit C/g ES) and for a significant decrease in malondialdehyde MDA (< 0.001) concentration. Zinc (25 mG/Kg), Iron (256 mG/Kg), Selenium (1.24 mG/Kg), Manganese (23mG/Kg) and Copper (28.95 mG/Kg) reinforce this antioxidant power because they are cofactors of enzymes (Superoxide dismutase, Peroxidase, Catalase) which ensure the fight against free radicals. The presence of phycocyanin is an asset for the anti-inflammatory action. The significant decrease in IL-8 (p < 0.001) and TNF alpha (p < 0.04) levels confirms this property. On the other hand, the nonsignificant increase in Il-6 (1.56 to 2.18 pg/m;p > 0.05) would be partly responsible for the rise in CD4 levels (p < 0.001) and the reduction in viral load in immune deficiency patients (p = 0.000) supplemented with spirulina. In conclusion, S. platensis from Nomayos by its antioxidant, anti-inflammatory and immuno-stimulatory properties would be a good supplement food for subjects at risk of developing severe forms of COVID-19.

Synergistically functionalized molybdenum disulfide-reduced graphene oxide nanohybrid based ultrasensitive electrochemical immunosensor for real sample analysis of COVID-19.

Herein, we have proposed a straightforward and label-free electrochemical immunosensing strategy supported on a glassy carbon electrode (GCE) modified with a biocompatible and conducting biopolymer functionalized molybdenum disulfide-reduced graphene oxide (CS-MoS2/rGO) nanohybrid to investigate the SARS-CoV-2 virus. CS-MoS2/rGO nanohybrid-based immunosensor employs recombinant SARS-CoV-2 Spike RBD protein (rSP) that specifically identifies antibodies against the SARS-CoV-2 virus via differential pulse voltammetry (DPV). The antigen-antibody interaction diminishes the current responses of the immunosensor. The obtained results indicate that the fabricated immunosensor is extraordinarily capable of highly sensitive and specific detection of the corresponding SARS-CoV-2 antibodies with a LOD of 2.38 zg mL-1 in phosphate buffer saline (PBS) samples over a broad linear range between 10 zg mL-1-100 ng mL-1. In addition, the proposed immunosensor can detect attomolar concentrations in spiked human serum samples. The performance of this immunosensor is assessed using actual serum samples from COVID-19-infected patients. The proposed immunosensor can accurately and substantially differentiate between (+) positive and (-) negative samples. As a result, the nanohybrid can provide insight into the conception of Point-of-Care Testing (POCT) platforms for cutting-edge infectious disease diagnostic methods.

Metamaterial enhanced novel plasmonic biosensor for specific detection of SARS-CoV-2 spike protein

In this study, we theoretically propose a surface plasmon resonance (SPR) biosensor composed of a plasmonic gold film, double negative (DNG) metamaterial, graphene-MoS2-COOH Van der Waals heterostructures and gold nanoparticles (Au NPs). We use a novel scheme of Goos-Hanchen (GH) shift to study the biosensing performances of our proposed plasmonic biosensor. The calculation results show that, both an extreme low reflectivity of 8.52×10-10 and significantly enhanced GH sensitivity of 2.1530×107 μm/RIU can be obtained, corresponding to the optimal configuration: 32 nm Au film/120 nm metamaterial/4-layer graphene/4-layer MoS2-COOH. In addition, there is a theoretically excellent linear response between the concentration of target analytes (SARS-CoV-2 and S protein) and the change in differential GH shift. Our proposed biosensor promises to be a useful tool for performing the novel coronavirus detection. © 2023 SPIE.

Selected dechlorination of triclosan by high-performance g-C3N4/Bi2MoO6 composites: Mechanisms and pathways

Environmental-friendly and efficient strategies for triclosan (TCS) removal have received more attention. Influenced by COVID-19, a large amount of TCS contaminants were accumulated in medical and domestic wastewater discharges. In this study, a unique g-C3N4/Bi2MoO6 heterostructure was fabricated and optimized by a novel and simple method for superb photocatalytic dechlorination of TCS into 2-phenoxyphenol (2-PP) under visible light irradiation. The as-prepared samples were characterized and analyzed by XRD, BET, SEM, XPS, etc. The rationally designed g-C3N4/Bi2MoO6 (4:6) catalyst exhibited notably photocatalytic activity in that more than 95.5% of TCS was transformed at 180 min, which was 3.6 times higher than that of pure g-C3N4 powder. This catalyst promotes efficient photocatalytic electron-hole separation for efficient dechlorination by photocatalytic reduction. The samples exhibited high recyclable ability and the dechlorination pathway was clear. The results of Density Functional Theory calculations displayed the TCS dechlorination selectivity has different mechanisms and hydrogen substitution may be more favorable than hydrogen ion in the TCS dechlorination hydrogen transfer process. This work will provide an experimental and theoretical basis for designing high-performance photocatalysts to construct the systems of efficient and safe visible photocatalytic reduction of aromatic chlorinated pollutants, such as TCS in dechlorinated waters. © 2022 Elsevier Ltd

An ultra-sensitive luteolin sensor based on Co-doped nitrogen-containing carbon framework/MoS2−MWCNTs composite for natural sample detection

As a common antioxidant and antimicrobial agent in plants, luteolin has a variety of pharmacological activities and biological effects, the ability to specifically bind proteins and thus inhibit novel coronaviruses and treat asthma. Here, Co doped nitrogen-containing carbon frameworks/MoS2−MWCNTs (Co@NCF/MoS2−MWCNTs) nanocomposites have been synthesized and successfully applied to electrochemical sensors. X-ray photoelectron spectroscopy, scanning electron microscopy and X-ray diffraction were used to examine the morphology and structure of the samples. Meanwhile, the electrochemical behavior of Co@NCF/MoS2−MWCNTs was investigated. Due to its excellent electrical conductivity, electrocatalytic activity and adsorption, it is used for the detection of luteolin. The Co@NCF/MoS2−MWCNTs/GCE sensor can detect luteolin in a linear range from 0.1 nM to 1.3 μM with a limit of detection of 0.071 nM. Satisfactory results were obtained for the detection of luteolin in natural samples. In addition, the redox mechanism and electrochemical reaction sites of luteolin were investigated by the scan rate of CV curves and density functional theory. This work demonstrates for the first time the combination of ZIF-67-derived Co@NCF and MoS2−MWCNTs as electrochemical sensors for the detection of luteolin, which opens a new window for the sensitive detection of luteolin. © 2022 Elsevier Ltd

Surface control approach for growth of cerium oxide on flower-like molybdenum disulfide nanosheets enables superior removal of uremic toxins

Due to the high incidence of kidney disease, there is an urgent need to develop wearable artificial kidneys. This need is further exacerbated by the coronavirus disease 2019 pandemic. However, the dialysate regeneration system of the wearable artificial kidney has a low adsorption capacity for urea, which severely limits its application. Therefore, nanomaterials that can effectively remove uremic toxins, especially urea, to regenerate dialysate are required and should be further investigated and developed. Herein, flower-like molybdenum disulphide (MoS2) nanosheets decorated with highly dispersed cerium oxide (CeO2) were prepared (MoS2/CeO2), and their adsorption performances for urea, creatinine, and uric acid were studied in detail. Due to the open interlayer structures and the combination of MoS2 and CeO2, which can provide abundant adsorption active sites, the MoS2/CeO2 nanomaterials present excellent uremic toxin adsorption activities. Further, uremic toxin adsorption capacities were also assessed using a self-made fixed bed device under dynamic conditions, with the aim of developing MoS2/CeO2 for the practical adsorption of uremic toxins. In addition, the biocompatibility of MoS2/CeO2 was systematically analyzed using hemocompatibility and cytotoxicity assays. Our data suggest that MoS2/CeO2 can be safely used for applications requiring close contact with blood. Our findings confirm that novel 2-dimensional nanomaterial adsorbents have significant potential for dialysis fluid regeneration. © 2022

Synthesis of active-site rich molybdenum-doped manganese tungstate nanocubes for effective electrochemical sensing of the antiviral drug (COVID-19) nitazoxanide.

Nitazoxanide (NTZ), a promising antiviral agent, is currently being tested in clinical trials as a potential treatment for novel coronavirus disease 2019 (COVID -19). This paper describes a one-pot hydrothermal synthesis to prepare molybdenum (Mo)-doped manganese tungstate nanocubes (Mo-MnWO4 NCs) for the electrochemical sensing of NTZ. The as-prepared Mo-MnWO4 NCs were characterized using various techniques such as XRD, Raman, FE-SEM, FE-TEM, and XPS to confirm the crystal structure, morphology, and elemental composition. The obtained results demonstrate that Mo doping on MnWO4 generates many vacancy sites, exhibiting remarkable electrochemical activity. The kinetic parameters of the electrode modified with Mo-MnWO4 NCs were calculated to be (Ks) 1.1 × 10-2 cm2 s-1 and (α) 0.97, respectively. Moreover, a novel electrochemical sensor using Mo-MnWO4 NCs was fabricated to detect NTZ, which is used as a primary antibiotic to control COVID-19. Under optimal conditions, the electrochemical reduction of NTZ was determined with a low detection limit of 3.7 nM for a linear range of 0.014-170.2 µM with a high sensitivity of 0.78 µA µM-1 cm-2 and negligible interference with other nitro group-containing drugs, cations, and anions. The electrochemical sensor was successfully used to detect NTZ in the blood serum and urine samples and achieved high recoveries in the range of 94-99.2% and 95.3-99.6%, respectively. This work opens a way to develop high-performance sensing materials by exploring the introduction of defect engineering on metal tungstates to detect drug molecules for practical applications.

Last year challenge of Nuclear Medicine: medical radioisotopes supply

Aim/Introduction: 99mTc is used in about 80% of the convencional diagnostic nuclear imaging procedures and represent yearly approximately 30 million examinations/year worldwide a year in diagnostic tests in hospitals, among others by oncology, cardiology and neurology.The production of radiopharmaceuticals for use in Nuclear Medicine has a complex system. It involves carefully calculated production schedules that take into account supply, demand and many logistical operations.The aim of this study is to show how our nuclear medicine department manage the impact of the shortly 99Mo supply chain and consequently, in the 99mTc availability and other radiopharmaceuticals produced in nuclear reactora. Material(s) and Method(s): European nuclear medicine organizations had just pay attention to how the COVID-19 pandemic might affect different parts of the 99Mo supply chain when had to dealt again faced with a new problem;the shortness 99Mo production. There are only five nuclear reactors involved in the production of 99Mo on industrial scale. These aging reactors are subject to unscheduled shutdowns and longer maintenance periods making the 99Mo supply chain vulnerable. In the last few months at our nuclear medicine department we had to reinvent ourselves so as not to completely stop carrying out the previously scheduled exams and therapies. Result(s): The use of technetium generators in Europe represents about 17% - 25% of the worldwide consumption of 99Mo, representing 30,000 exams per day and about 1.1 million doses per month. The main consequences at the IPO-Porto was;Delays in diagnosis/staging, rescheduling exams, change of surgery dates (Sentinel Ganglion and Myocardial Perfusion Cardiacs), weeks of overbooking, delay in follow-up of Glomerular Filtration Rate in pre- or post-transplant patients, postponement of 131I Therapies, Scintigraphy and Whole Body Scintigraphy in patients who were already in hypothyroidism. we had to reinvent the use of 99mTc generators, change exams appointments times, reagroup exams types by defined days and other radiopharmaceutical management tools that were not commonly used. Conclusion(s): Approximately 2/3 of scheduled exams were postponed and we had to deal with weekly and daily stock updates. Our department suggest some measures and procedures that could help with future 99Mo shortages, in order to be ready in future situations and to avoid shortness of production: the creation of a centralized European radiopharmacy system, European policies to encourage long-term investment, homogenization of marketing specifications in the Member States, solid databases of radiopharmaceuticals used/ available in Europe and encouraging cooperation between other countries outside the European Union.

Surface control approach for growth of cerium oxide on flower-like molybdenum disulfide nanosheets enables superior removal of uremic toxins

Due to the high incidence of kidney disease, there is an urgent need to develop wearable artificial kidneys. This need is further exacerbated by the coronavirus disease 2019 pandemic. However, the dialysate regeneration system of the wearable artificial kidney has a low adsorption capacity for urea, which severely limits its application. Therefore, nanomaterials that can effectively remove uremic toxins, especially urea, to regenerate dialysate are required and should be further investigated and developed. Herein, flower-like molybdenum disulphide (MoS2) nanosheets decorated with highly dispersed cerium oxide (CeO2) were prepared (MoS2/CeO2), and their adsorption performances for urea, creatinine, and uric acid were studied in detail. Due to the open interlayer structures and the combination of MoS2 and CeO2, which can provide abundant adsorption active sites, the MoS2/CeO2 nanomaterials present excellent uremic toxin adsorption activities. Further, uremic toxin adsorption capacities were also assessed using a self-made fixed bed device under dynamic conditions, with the aim of developing MoS2/CeO2 for the practical adsorption of uremic toxins. In addition, the biocompatibility of MoS2/CeO2 was systematically analyzed using hemocompatibility and cytotoxicity assays. Our data suggest that MoS2/CeO2 can be safely used for applications requiring close contact with blood. Our findings confirm that novel 2-dimensional nanomaterial adsorbents have significant potential for dialysis fluid regeneration.

Screening for Covid-19 with cellular morphometric parameters on the routine hematology analyzer DXH 800

Background-aim: Coronavirus disease (COVID-19) caused by SARS-CoV-2 is characterized by high contagiousness requiring isolation measures. Currently, diagnosis is based on the RT-PCR and/or chest computed tomography (CT) scan, but these methodologies are time-consuming and may delay the diagnosis. CBC-Diff analysis is the first step in patient assessment and may contribute to the diagnosis of COVID-19. Morphological changes of the immune cells can be identified by electro-optical analysis on the hematology analyzer DxH 800 (Beckman Coulter, Inc., Brea, CA). We studied whether the analysis of cellular population data (CPD), provided as part of CBC-Diff analysis by the DxH 800 analyzers can help to identify SARS-CoV-2 infection. Methods: The study included 322 consecutive patients from the emergency unit with positive RT-PCR (Allplex 2019 nCoV Assay, Eurobio, Les Ulis, France) and 285 consecutive patients with clinical suspicion for COVID-19, but who had negative RT-PCR and CT-scan not suggestive of SARS-CoV-2 infection. We also included 137 subjects with a normal CBC-Diff, referred to our institution without evidence of infection and when prevalence of SARS-CoV-2 was very low in France. Blood was collected in EDTA-K3 tubes and analyzed within 6 h after collection. Results: The majority of CPD was different between the 3 groups;CPD of patients (with or without COVID-19) were significantly different of CPD of controls. Four, six and nine CPD for NE, LY, and MO, respectively, were significantly different between COVID-19+ and COVID-19- patients. Using ROC analysis, we identified parameters, which were able to discriminate COVID-19+ patients from COVID-19- patients. The best parameter was SD-V-Mo (Standard Deviation of Monocyte Volume), with AUC 0.819, sensitivity of 91.59% and specificity of 63.03% at the cut-off>21.71. MN-V-Mo (Mean Monocyte Volume) demonstrated AUC 0.742 with sensitivity of 76.64%, specificity of 65.85% at cut-off>180. SD-AL2-MO (Standard Deviation of Axial Light Loss for Monocytes) provided AUC 0.722 with sensitivity of 85.67%, specificity of 52.11% at cut-off>17.51. Currently CPD are research use only;their clinical utility has not been established. Conclusions: Consideration of CPD could constitute a first step and potentially aid in the early diagnosis of COVID-19.

Synthesis of flower-like MoS2/CNTs nanocomposite as an efficient catalyst for the sonocatalytic degradation of hydroxychloroquine.

Contamination of water resources by pharmaceutical residues, especially during the time of pandemics, has become a serious problem worldwide and concerns have been raised about the efficient elimination of these compounds from aquatic environments. This study has focused on the development and evaluation of the sonocatalytic activity of a flower-like MoS2/CNTs nanocomposite for the targeted degradation of hydroxychloroquine (HCQ). This nanocomposite was prepared using a facile hydrothermal route and characterized with various analytical methods, including X-ray diffraction and electron microscopy, which results confirmed the successful synthesis of the nanocomposite. Moreover, the results of the Brunauer-Emmett-Teller and diffuse reflectance spectroscopy analyses showed an increase in the specific surface area and a decrease in the band gap energy of the nanocomposite when compared with those of MoS2. Nanocomposites with different component mass ratios were then synthesized, and MoS2/CNTs (10:1) was identified to have the best sonocatalytic activity. The results indicated that 70% of HCQ with the initial concentration of 20 mg/L could be degraded using 0.1 g/L of MoS2/CNTs (10:1) nanocomposite within 120 min of sonocatalysis at the pH of 8.7 (natural pH of the HCQ solution). The dominant reactive species in the sonocatalytic degradation process were identified using various scavengers and the intermediates generated during the process were detected using GC-MS analysis, enabling the development of a likely degradation scheme. In addition, the results of consecutive sonocatalytic cycles confirmed the stability and reusability of this nanocomposite for sonocatalytic applications. Thus, our data introduce MoS2/CNTs nanocomposite as a proficient sonocatalyst for the treatment of pharmaceutical contaminants.

Renewable Hydrocarbon Production from Waste Cottonseed Oil Pyrolysis and Catalytic Upgrading of Vapors with Mo-Co and Mo-Ni Catalysts Supported on γ-Al2O3.

In this work, the production of renewable hydrocarbons was explored by the means of waste cottonseed oil (WCSO) micropyrolysis at 500 °C. Catalytic upgrading of the pyrolysis vapors was studied using α-Al2O3, γ-Al2O3, Mo-Co/γ-Al2O3, and Mo-Ni/γ-Al2O3 catalysts. The oxygen removal efficiency was much lower in non-catalytic pyrolysis (18.0%), whilst γ-Al2O3 yielded a very high oxygen removal efficiency (91.8%), similar to that obtained with Mo-Co/γ-Al2O3 (92.8%) and higher than that attained with Mo-Ni/γ-Al2O3 (82.0%). Higher conversion yields into total renewable hydrocarbons were obtained with Mo-Co/γ-Al2O3 (61.9 wt.%) in comparison to Mo-Ni/γ-Al2O3 (46.6%). GC/MS analyses showed a relative chemical composition of 31.3, 86.4, and 92.6% of total renewable hydrocarbons and 58.7, 7.2, and 4.2% of oxygenated compounds for non-catalytic bio-oil (BOWCSO), BOMoNi and BOMoCo, respectively. The renewable hydrocarbons that were derived from BOMoNi and BOMoCo were mainly composed by olefins (35.3 and 33.4%), aromatics (31.4 and 28.9%), and paraffins (13.8 and 25.7%). The results revealed the catalysts' effectiveness in FFA decarbonylation and decarboxylation, as evidenced by significant changes in the van Krevelen space, with the lowest O/C ratio values for BOMoCo and BOMoNi (O/C = 0-0.10) in relation to the BOWCSO (O/C = 0.10-0.20), and by a decrease in the presence of oxygenated compounds in the catalytic bio-oils.

Toward Urease-free Wearable Artificial Kidney: Widened Interlayer Spacing MoS2 Nanosheets with Highly Effective Adsorption for Uremic Toxins

The high incidence of kidney disease caused by various factors (such as COVID-19) has triggered an extreme desire for wearable artificial kidney (WAK). Nevertheless, the dialysate regeneration system in WAK presents a very low adsorption capacity of urea, and must rely on the help of urease and zirconium compounds, which make the device too complex and costly, thus limiting their application. In this study, we employ the adsorption activity of defect-rich MoS2 nanosheets with widened interlayer spacing (WDR-MoS2) for the elimination of three crucial uremic toxins (urea, creatinine, and uric acid). The high adsorption performances of WDR-MoS2 are owing to the presence of abundant S atoms between the two MoS2 sheets that can efficiently adsorb uremic toxins through the unique S-N bond. Furthermore, widening the layer spacing of MoS2 is similar to adjusting the aperture of a filter, which can not only speed up the transport of uremic toxins but also prevent the passage of large molecules (such as proteins). Thus, the WDR-MoS2 can neither affect cell viability nor produce hemolysis and coagulation in the blood. Finally, a home-made WDR-MoS2 fixed-bed system without urease and zirconium compounds is used to efficiently remove uremic toxins in the dialysate. WDR-MoS2 is expected to fundamentally solve the materials science challenges in WAK and provide a new design idea for the development of high-performance 2D material-based adsorbents.

Structural and tribological properties of the re-casted dental NiCrMo alloy

The crisis related to the COVID 19 pandemic caused an increase in nickel prices on the global markets. From this perspective, it seems promising to search for the possibilities of effective recycling of nickel-based alloys as biomaterials. The topic of the recasting of Ni-Cr dental alloys is currently being broadly described in the literature. Nonetheless, there are still no conclusive results on the impact of recasting on the quality of the cast dentures. Considering the aforementioned, for research, the effect of recasting on the wear resistance and microstructure of NiCrMo dental alloy was investigated. The Heraenium NA alloy was used for testing. Abrasion resistance was tested by the ball on disc method. Microstructure and wear trace were observed using an optical microscope and a scanning electron microscope. The tests showed a higher wear resistance of the re-casted material. The average coefficient of friction for the initially cast alloys was 0.664, while for the remelted samples the mean value was 0.441. The tested samples are characterised by an abrasive-adhesive wear mechanism. Piling up of the wear tracks edges was observed - the highest for H100. For the H100 samples, a slightly lower average hardness value (HV10) was observed - 226 compared to 233 (HV10) for the samples made from the re-casted alloy (H0). The presence of a dendritic structure of alloys was demonstrated. Blocky eutectic precipitations are visible against the matrix. The observed growth of interdendritic precipitations constitute a natural barrier for the counterpart material and increases its tribological properties. Obtained results suggest that alloy recasting does not constitute a limitation to its use. © 2021 Institute of Physics Publishing. All rights reserved.

Sensitive and quantitative detection of SARS-CoV-2 antibodies from vaccinated serum by MoS2-field effect transistor

Recently, the coronavirus disease (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread globally with major impact on public health. Novel methods that enable fast and efficient detection of the virus and the associated biomarkers, such as SARS-CoV-2 antibodies, may provide alterative opportunities for early diagnosis, disease status monitoring, and the development of vaccines. Here, we report the fabrication of a functionalized MoS2-field effect transistor (FET) for sensitive and quantitative detection of antibodies against SARS-CoV-2 spike protein receptor binding domain (S-RBD) in vaccinated serum specimens. The device was modified by SARS-CoV-2 S-RBD fusion protein on the surface and enabled rapid detection of SARS-CoV-2 antibodies. In addition, an on-chip calibration method was established for quantitative measurement. Furthermore, this method was applied to measure the levels of S-RBD antibodies in serum specimens from vaccinated donors. The devices showed no response to negative control samples from individuals who did not receive vaccination, suggesting the high specificity of this method. This study illustrated the successful fabrication of S-RBD functionalized MoS2-FET with potential clinical applications to facilitate vaccine development and efficacy evaluation.

Molybdenum Carbonyl Complexes with Benzimidazole Derivatives Against SARS-CoV-2 by Molecular Docking and DFT/TDDFT Methods

Benzimidazole derivative molecules attract attention of scientists due to their bioactivities. The dramatic changes in recorded activities according to the type and position of the substituents motivate synthesis and analysis of new molecules. Commercial benzimidazole-based molecules have been used in therapeutic procedures. It is known that the activities of metal complexes with benzimidazole derivative ligands have different activities when compared to the benzimidazole main structure. Nowadays, one of the most important health problems is COVID-19, which caused the pandemic that we are still experiencing. Although vaccine studies are important to overcome acute problems, regarding the possible post-vaccination adverse effects, the need for new drugs against the virus is obvious. Considering the urgency and the limited facilities during the pandemic, preliminary in silico studies of candidate molecules are essential. In this study, {[bis-(N-benzylbenzimidazole)] tetracarbonylmolybdenum}, {[bis-(N-4-chlorobenzylbenzimidazole)] tetracarbonylmolybdenum} and {[bis-(N-4-methoxybenzylbenzimidazole)] tetracarbonylmolybdenum} were synthesized and characterized. The optimization and the structural analysis of these molecules were performed by DFT/TDDFT methods. The molecules were docked into SARS coronavirus main peptidase (PDB ID: 2gtb), COVID-19 main protease in complex with Z219104216 (PDB ID: 5r82), COVID-19 main protease in complex with an inhibitor N3 (PDB ID: 6lu7) and Papain-like protease of SARS-CoV-2 (PDB ID: 6w9c) crystal structures for evaluation of their anti-viral activity. Molybdenum carbonyl complexes containing benzimidazole derivative ligands have been synthesized, characterized, and analyzed structurally by DFT/TDDFT methods. Antiviral activities of the complexes were analyzed by molecular docking methods against some important Coronavirus targets in parallel with the pandemic period we are living in. Inhibitory potency of the complexes toward COVID-19 targeted is compared to some well-known commercial antivirals.

A Phase I/II Study of Twice Weekly Ixazomib Plus Pomalidomide and Dexamethasone in Relapsed and Refractory Multiple Myeloma

Introduction: Ixazomib is an oral proteasome inhibitor (PI) that is currently approved to be administered once weekly in combination with lenalidomide (LEN) and dexamethasone in RRMM (Moreau et al N Eng J Med 2016;374:1621-1634). As most patients are LEN refractory at the time of first relapse, pomalidomide-based regimens are commonly utilized due to their proven efficacy in this population. We hypothesized that twice weekly dosing of ixazomib may be more efficacious as this has been previously studied as monotherapy (Richardson et al, Blood 2014 Aug 14;124(7):1038-46) and in combination with LEN demonstrating promising activity and safety (Richardson et al, Br J Haematol. 2018 Jul;182(2):231-244). We present results of our phase I/II trial of twice weekly ixazomib in combination with pomalidomide and dexamethasone in RRMM, including the recommended phase II dose and first report of efficacy of this combination. Methods: This is a phase I/II multicenter, single-arm, open label study evaluating the combination of twice weekly ixazomib with pomalidomide and dexamethasone in RRMM. The primary objective for phase I portion is to determine safety and the maximum tolerated dose (MTD) of this combination using a standard 3+3 dose escalation design and primary objective of the phase II portion is overall response rate (ORR) with secondary outcomes including progression-free survival (PFS) and clinical benefit rate (CBR) Ixazomib is studied at doses of 3mg or 4mg on days 1, 4, 8, 11, pomalidomide at a dose of 2mg, 3mg and 4mg on days 1-14 and dexamethasone is administered at a dose of 12mg on days 1, 2, 4, 5, 8, 9, 11, 12 (8mg for patients > 75 years old) on a 21 day cycle (Table 1). Patients were included if they received 2 prior lines of therapy, but 1 prior line was allowed if first line treatment included a PI and an immunomodulatory agent and disease relapse occurred within 60 days of last therapy. Patients who were ixazomib exposed or pomalidomide refractory were excluded. Results: At the time of data cutoff, 22 patients have been enrolled across all cohorts. There were two dose-limiting toxicities (DLT) noted during the dose escalation phase (upper respiratory infection and neutropenia, respectively) establishing the RP2D of 4mg ixazomib and 4mg pomalidomide. Median age at the time of enrollment was 68 years old with ISS stage at diagnosis of I (14%), II (32%), and III (23%). High-risk FISH abnormalities were seen in 43% of patients as follows: del 17p (9%), gain 1q (36%), t(4;14) (5%), t(14;16) (9%). Median prior lines of therapy was 2 (range 1-4) with 100% of patients having prior treatment with lenalidomide and 95% with prior bortezomib. Fifty-nine percent of patients had a prior autologous stem cell transplant. Ten patients have been enrolled at the RP2D at the time of data cut off. The most common treatment-related toxicities were mainly low grade (Grade 1-2) and included neutropenia (45%), lower extremity edema (41%), insomnia (36%), dyspnea (32%) and weight gain (32%). Grade 3 or greater toxicities were noted in 36% of patients and included neutropenia (18%), thrombocytopenia (5%), anemia (5%), atrial fibrillation (5%), dehydration (5%), diarrhea (5%), fall (5%), lung infection (5%), and pneumonitis (5%). Dose reductions occurred in 13 patients and predominantly involved dexamethasone due to weight gain, insomnia, atrial fibrillation and fatigue. There have been no discontinuations due to toxicity and no treatment related mortality at the time of data cutoff. The ORR in all cohorts was 45%, with 9% achieving sCR, 9% VGPR and 86% achieving stable disease or better. At the RP2D, the ORR was 50% with 30% of patients achieving VGPR or better. At the median follow up of 10 months, median PFS was 13 months (95% CI: 11-NR) and median overall survival was not reached. Conclusions: Twice weekly ixazomib in combination with pomalidomide and dexamethasone is a generally well-tolerated regimen with promising activity. The recommended phase II dose has been established at 4mg of ixazomib and 4mg of pomalidomide demonstrat ng efficacy in a high-risk cohort of RRMM patients. The all-oral nature of this regimen has allowed for robust accrual during the COVID 19 pandemic. [Formula presented] Disclosures: Nadeem: BMS: Membership on an entity's Board of Directors or advisory committees;Karyopharm: Membership on an entity's Board of Directors or advisory committees;GSK: Membership on an entity's Board of Directors or advisory committees;Takeda: Membership on an entity's Board of Directors or advisory committees;Adaptive Biotechnologies: Membership on an entity's Board of Directors or advisory committees. Mo: Karyopharm: Honoraria, Membership on an entity's Board of Directors or advisory committees;Janssen: Honoraria;GSK: Consultancy, Membership on an entity's Board of Directors or advisory committees;Epizyme: Consultancy;Eli Lilly: Consultancy;BMS: Membership on an entity's Board of Directors or advisory committees;Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees;AbbVIE: Consultancy. Bianchi: Jacob D. Fuchsberg Law Firm: Consultancy;MJH: Honoraria;Karyopharm: Consultancy, Honoraria;Pfizer: Consultancy, Honoraria. Sanchorawala: Celgene: Research Funding;Pfizer: Honoraria;Sorrento: Research Funding;Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding;Takeda: Research Funding;Prothena: Membership on an entity's Board of Directors or advisory committees, Research Funding;Abbvie: Membership on an entity's Board of Directors or advisory committees;Caelum: Membership on an entity's Board of Directors or advisory committees, Research Funding;Regeneron: Membership on an entity's Board of Directors or advisory committees;Proclara: Membership on an entity's Board of Directors or advisory committees;Oncopeptide: Research Funding;Karyopharm: Research Funding. Sperling: Adaptive: Consultancy. Munshi: Janssen: Consultancy;Takeda: Consultancy;Bristol-Myers Squibb: Consultancy;Celgene: Consultancy;Amgen: Consultancy;Karyopharm: Consultancy;Oncopep: Consultancy, Current equity holder in publicly-traded company, Other: scientific founder, Patents & Royalties;Legend: Consultancy;Abbvie: Consultancy;Adaptive Biotechnology: Consultancy;Novartis: Consultancy;Pfizer: Consultancy. Ghobrial: AbbVie, Adaptive, Aptitude Health, BMS, Cellectar, Curio Science, Genetch, Janssen, Janssen Central American and Caribbean, Karyopharm, Medscape, Oncopeptides, Sanofi, Takeda, The Binding Site, GNS, GSK: Consultancy. Anderson: Sanofi-Aventis: Membership on an entity's Board of Directors or advisory committees;Pfizer: Membership on an entity's Board of Directors or advisory committees;Janssen: Membership on an entity's Board of Directors or advisory committees;Gilead: Membership on an entity's Board of Directors or advisory committees;Millenium-Takeda: Membership on an entity's Board of Directors or advisory committees;Celgene: Membership on an entity's Board of Directors or advisory committees;Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees;AstraZeneca: Membership on an entity's Board of Directors or advisory committees;Scientific Founder of Oncopep and C4 Therapeutics: Current equity holder in publicly-traded company, Current holder of individual stocks in a privately-held company;Mana Therapeutics: Membership on an entity's Board of Directors or advisory committees. Richardson: AbbVie: Consultancy;Karyopharm: Consultancy, Research Funding;Janssen: Consultancy;Protocol Intelligence: Consultancy;Takeda: Consultancy, Research Funding;GlaxoSmithKline: Consultancy;Regeneron: Consultancy;Secura Bio: Consultancy;Sanofi: Consultancy;AstraZeneca: Consultancy;Celgene/BMS: Consultancy, Research Funding;Oncopeptides: Consultancy, Research Funding;Jazz Pharmaceuticals: Consultancy, Research Funding.

Improved Quality of Life (QOL) with Lisocabtagene Maraleucel (liso-cel), a CD19-Directed Chimeric Antigen Receptor (CAR) T Cell Therapy, Compared with Standard of Care (SOC) As Second-Line (2L) Treatment in Patients (Pts) with Relapsed or Refractory (R/R) Large B-Cell Lymphoma (LBCL): Results from the Phase 3 Transform Study

Background: Pts with previously treated R/R aggressive LBCL have compromised health-related QOL (HRQOL). Liso-cel is an autologous, CD19-directed, defined composition, 4-1BB CAR T cell product administered at equal target doses of CD8 + and CD4 + CAR + T cells. In a prespecified interim analysis of TRANSFORM (NCT03575351), a randomized, open-label, pivotal trial, liso-cel demonstrated statistically significant and clinically meaningful improvement in the primary endpoint of event-free survival and key secondary endpoints (complete response rate and progression-free survival) in adults with R/R LBCL after failure of first-line (1L) immunochemotherapy compared with SOC, with no new safety signals. Here we present results of the pt-reported outcomes (PRO) analysis from TRANSFORM. Methods: Adults (age ≤ 75 yrs) with R/R LBCL (≤ 12 mo after 1L therapy), who were eligible for autologous stem cell transplantation (ASCT), were randomized to receive either SOC (3 cycles of salvage chemotherapy [CT] and BEAM + ASCT for responding pts) or liso-cel after lymphodepletion. Crossover to receive liso-cel was allowed in the SOC arm for pts who failed treatment. The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - 30 items (EORTC QLQ-C30) and the Functional Assessment of Cancer Therapy - Lymphoma Subscale (FACT-LymS) were administered at randomization (baseline) and on Days 29 (infusion of liso-cel or 2 cycles of salvage CT), 64 (1 mo post liso-cel or completion of CT), 126 (3 mos post liso-cel or 2 mos post ASCT), and Mo 6 and other prespecified timepoints up to Mo 36 or end of study. No PRO data were collected after crossover. The analysis was based on the PRO-evaluable population (pts with a baseline and ≥ 1 post-baseline assessment). Predefined thresholds determined clinically meaningful changes. Global health/QOL (GH/QOL), physical functioning, cognitive functioning, fatigue, pain, and FACT-LymS were the primary domains of interest based on their relevance to the study population and treatment. A linear mixed model for repeated measures (MMRM) analysis was performed to assess the between-treatment difference in overall least squares (LS) mean change from baseline for each primary domain, using data collected up to Day 126 for visits with a sample size per arm ≥ 10. Proportions of pts with meaningful change from baseline were assessed for each primary domain up to Mo 6. All analyses were descriptive only. Results: Of 184 randomized pts, 90 (49%) and 85 (46%), respectively, were included in the PRO-evaluable population for the EORTC QLQ-C30 (SOC vs liso-cel n=43 vs 47) and FACT-LymS (n=40 vs 45, respectively). The PRO assessment completion rate from baseline up to Mo 6 was ≥ 45%, which was lower than expected primarily due to operational challenges during the COVID-19 pandemic but was comparable for both arms. In the MMRM analysis, the liso-cel arm had more favorable overall LS mean changes from baseline to Day 126 than the SOC arm in most of the EORTC QLQ-C30 domains and FACT-LymS. In particular, the between-treatment differences for cognitive functioning (−2.09 vs 2.21) and fatigue (3.75 vs −1.95) for SOC versus liso-cel, respectively, exceeded the prespecified minimal important difference threshold (Table);in those domains, the SOC arm deteriorated while the liso-cel arm improved. In individual-level analyses, the proportion of pts with meaningful improvement for fatigue and GH/QOL was higher, while deterioration was lower, in the liso-cel arm versus SOC arm from baseline up to Mo 6 (Figure). At Mo 6, a higher proportion of pts experienced worsened fatigue (71% vs 18%) and a lower proportion experienced improved fatigue (29% vs 47%) in the SOC arm compared with the liso-cel arm;for GH/QOL, a higher proportion of pts worsened (57% vs 18%) and lower proportion improved (14% vs 53%), respectively. For the other primary domains, the proportions of pts with improvement or deterioration favored liso-cel or were similar between arms. Conclusions: Compared with SOC, liso-cel sh wed favorable improvement in most primary PRO domains, particularly EORTC QLQ-C30 cognitive functioning and fatigue and more pts showed PRO improvements and fewer showed deterioration by Mo 6 with liso-cel. The results were achieved despite only responders remaining in the SOC arm after salvage CT. HRQOL was either improved or maintained after liso-cel treatment in pts with R/R LBCL after failure of 1L therapy. [Formula presented] Disclosures: Abramson: Bristol-Myers Squibb Company: Consultancy, Research Funding;Morphosys: Consultancy;C4 Therapeutics: Consultancy;Kite Pharma: Consultancy;Kymera: Consultancy;Incyte Corporation: Consultancy;Bluebird Bio: Consultancy;Astra-Zeneca: Consultancy;Allogene Therapeutics: Consultancy;Novartis: Consultancy;EMD Serono: Consultancy;Genmab: Consultancy;Seagen Inc.: Research Funding;AbbVie: Consultancy;Karyopharm: Consultancy;Genentech: Consultancy;BeiGene: Consultancy. Arnason: Juno/BMS: Honoraria. Glass: BMS: Consultancy;Roche: Consultancy, Research Funding, Speakers Bureau;Riemser: Research Funding;Kite: Consultancy;Novartis: Consultancy;Helios Klinik Berlin-Buch: Current Employment. Crotta: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Montheard: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Previtali: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Liu: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Braverman: BMS: Current Employment, Current equity holder in publicly-traded company. Guo: Daiichi Sankyo: Consultancy;UCB: Consultancy;Janssen: Consultancy;Gilead: Consultancy;Bristol Myers Squibb: Consultancy;EMD Serono: Consultancy;Evidera: Current Employment. Shi: Bristol Myers Squibb: Consultancy. Kamdar: ADC Therapeutics: Consultancy;Adaptive Biotechnologies: Consultancy;TG Therapeutics: Research Funding;Genentech: Research Funding;AbbVie: Consultancy;KaryoPharm: Consultancy;Kite: Consultancy;AstraZeneca: Consultancy;SeaGen: Speakers Bureau;Celgene: Other;Genetech: Other;Celgene (BMS): Consultancy.

Clinical trials and tribulations: the ordeals of setting up a high intensity clinical trial during COVID19 times

We present our experience with the urgent set-up and execution of a phase 2/3 study to evaluate an investigational medicinal product (ORGN001) in Molybdenum cofactor deficiency type A (MoCDA).MoCDA is a rare inborn error of molybdenum cofactor production resulting in rapidly progressive fatal neurologic damage during the neonatal period. ORGN001 replaces the missing substrate restoring MoCo biosynthesis. It is administered as a daily IV infusion with the first dose given as soon as feasible.A potential subject was identified by prenatal genetic testing on week 12 of pregnancy and was born at 37 weeks via elective C-section. Obstetrics, neonatology and emergency transfer teams were arranged in advance in the local hospital. She was transferred within two hours of birth and was given the first dose of IMP at five hours of life.The set-up of the trial (including R&D approvals) was finalised four weeks before expected birth date in case of prematurity. Early conversations with the intensive care ward ensured appropriate bed space and an admission plan integrating research activities with standard of care. The need for urgent treatment meant careful planning of nursing, pharmacy and medical resources including set up of an on-call rota, training in study protocol and manipulation/administration of the investigational product, and timely EPIC build for prescription and trial specific templates.This is the first time that the Metabolic team takes the lead on a clinical trial of this magnitude providing ad hoc experimental treatment for one patient. Coordination of a multicentre multidisciplinary team in the midst of the COVID19 pandemic was in itself a considerable achievement. Everyone involved was essential to complete the study and achieve the best possible result.The successful execution of this clinical trial shows the adaptation capacity and resilience of GOSH as a research hospital during these difficult times.

3D Printed Cobalt-Chromium-Molybdenum Porous Superalloy with Superior Antiviral Activity.

COVID-19 pandemic and associated supply-chain disruptions emphasise the requirement for antimicrobial materials for on-demand manufacturing. Besides aerosol transmission, SARS-CoV-2 is also propagated through contact with virus-contaminated surfaces. As such, the development of effective biofunctional materials that can inactivate SARS-CoV-2 is critical for pandemic preparedness. Such materials will enable the rational development of antiviral devices with prolonged serviceability, reducing the environmental burden of disposable alternatives. This research reveals the novel use of Laser Powder Bed Fusion (LPBF) to 3D print porous Cobalt-Chromium-Molybdenum (Co-Cr-Mo) superalloy with potent antiviral activity (100% viral inactivation in 30 min). The porous material was rationally conceived using a multi-objective surrogate model featuring track thickness (tt) and pore diameter (ϕd) as responses. The regression analysis found the most significant parameters for Co-Cr-Mo track formation to be the interaction effects of scanning rate (Vs) and laser power (Pl) in the order PlVs>Vs>Pl. Contrastively, the pore diameter was found to be primarily driven by the hatch spacing (Sh). The study is the first to demonstrate the superior antiviral properties of 3D printed Co-Cr-Mo superalloy against an enveloped virus used as biosafe viral model of SARS-CoV-2. The material significantly outperforms the viral inactivation time of other broadly used antiviral metals such as copper and silver, as the material's viral inactivation time was from 5 h to 30 min. As such, the study goes beyond the current state-of-the-art in antiviral alloys to provide extra protection to combat the SARS-CoV-2 viral spread. The evolving nature of the COVID-19 pandemic brings new and unpredictable challenges where on-demand 3D printing of antiviral materials can achieve rapid solutions while reducing the environmental impact of disposable devices.