44 research outputs found

    A community effort in SARS-CoV-2 drug discovery.

    Get PDF
    peer reviewedThe COVID-19 pandemic continues to pose a substantial threat to human lives and is likely to do so for years to come. Despite the availability of vaccines, searching for efficient small-molecule drugs that are widely available, including in low- and middle-income countries, is an ongoing challenge. In this work, we report the results of an open science community effort, the "Billion molecules against Covid-19 challenge", to identify small-molecule inhibitors against SARS-CoV-2 or relevant human receptors. Participating teams used a wide variety of computational methods to screen a minimum of 1 billion virtual molecules against 6 protein targets. Overall, 31 teams participated, and they suggested a total of 639,024 molecules, which were subsequently ranked to find 'consensus compounds'. The organizing team coordinated with various contract research organizations (CROs) and collaborating institutions to synthesize and test 878 compounds for biological activity against proteases (Nsp5, Nsp3, TMPRSS2), nucleocapsid N, RdRP (only the Nsp12 domain), and (alpha) spike protein S. Overall, 27 compounds with weak inhibition/binding were experimentally identified by binding-, cleavage-, and/or viral suppression assays and are presented here. Open science approaches such as the one presented here contribute to the knowledge base of future drug discovery efforts in finding better SARS-CoV-2 treatments.R-AGR-3826 - COVID19-14715687-CovScreen (01/06/2020 - 31/01/2021) - GLAAB Enric

    Impact strength of underground cement materials

    No full text
    The article presents the results of a study of impact strength of underground cement materials with different water content activated by mixing water with the addition of high range plasticizers, biocidal agents, pigments, ground quartz, silica fume and fine aggregate. Samples for testing are formed in plates of size 150×100×10 mm. Testing was conducted at impact drop-weight method ASTM D7136. The maximum contact force, contact duration and magnitude of the pulse of the drummer were considered as the test parameters. The good results of the studied parameters showed highly filled plasticized compositions of the new generation. The use of iron oxide with yellow and green glauconitic pigments allows obtaining good results. Activation of the mixing water led to a rise in the maximum contact force in the case of the processing mode of E+М (3–3) while reducing the duration of the contact and the magnitude of the impulse. During the test of the biocidal composites with different biocidal preparations, it was established that the best indicators of the impact strength correspond to materials with the addition of «Teflex Antiplesen»

    The regioselective synthesis of spirooxindolo pyrrolidines and pyrrolizidines via three-component reactions of acrylamides and aroylacrylic acids with isatins and α-amino acids

    No full text
    The regioselective three-component condensation of azomethine ylides derived from isatins and α-amino acids with acrylamides or aroylacrylic acids as dipolarophiles has been realized through a one-pot 1,3-dipolar cycloaddition protocol. Decarboxylation of 2'-aroyl-2-oxo-1,1',2,2',5',6',7',7a'-octahydrospiro[indole-3,3'-pyrrolizine]-1'-carboxylic acids is accompanied by cyclative rearrangement with formation of dihydropyrrolizinyl indolones

    Vorontsovite, (Hg5cu)\u3a36TLAs4S12, and ferrovorontsovite, (Fe5Cu)\u3a36TlAs4S12: The Tl- and Tl-Fe-analogues of galkhaite from the vorontsovskoe gold deposit, northern Urals, Russia

    No full text
    Two new mineral species, vorontsovite, ideally (Hg5Cu)TlAs4S12, and ferrovorontsovite, ideally (Fe5Cu)TlAs4S12, the Tl- and Tl–Fe-analogues of galkhaite, respectively, have been discovered at the Vorontsovskoe gold deposit, Northern Urals, Russia. They occur as anhedral grains up to 0.5 mm (vorontsovite) and 0.2 mm (ferrovorontsovite) embedded in a calcite-dolomite matrix. The chemical composition of vorontsovite (wt %) is: Hg 35.70, Fe 5.36, Zn 1.26, Cu 3.42, Ag 0.64, Tl 11.53, Cs 0.35, Pb 0.04, As 15.98, Sb 2.35, Te 0.41, S 22.70, Se 0.02, total 99.76. The empirical formula, calculated on the basis of 23 atoms pfu, is: [(Hg3.02Fe1.63Zn0.33)Σ4.98(Cu0.91Ag0.10)Σ1.01](Tl0.96Cs0.04)Σ1.00(As3.62Sb0.33Te0.05)Σ4.00S12.01. The composition of ferrovorontsovite (wt %) is: Hg 25.13, Fe 9.89, Zn 1.16, Cu 3.95, Ag 0.45, Tl 12.93, Cs 0.44, Pb 0.04, As 17.83, Sb 2.15, Te 0.40, S 24.91, total 99.28. The empirical formula, calculated on the basis of 23 atoms pfu, is: [(Fe2.74Hg1.94Zn0.27)Σ4.95(Cu0.96Ag0.06)Σ1.02](Tl0.98Cs0.05)Σ1.03(As3.68Sb0.27Te0.05)Σ4.00S12.00. Both minerals are cubic, space group I-43m, with a = 10.2956(6) Å, V = 1091.3(1) Å3, Z = 2 (vorontsovite); and a = 10.2390(7) Å, V = 1073.43(22) Å3, Z = 2 (ferrovorontsovite). The crystal structures of both minerals were refined to R = 0.0376 (vorontsovite) and R = 0.0576 (ferrovorontsovite). Vorontsovite and ferrovorontsovite have been approved by the IMA-CNMNC under the numbers 2016-076 and 2017-007, respectively. The first one is named after the type locality, but also honors the mining engineer Vladimir Vasilyevich Vorontsov. The second is named for its chemical composition, as the Fe-analogue of the first. Both species are isostructural with galkhaite, being its Tl- and Tl–Fe analogues, respectively, and forming altogether the galkhaite group

    Академік Лазарян Всеволод Арутюнович

    No full text
    Академик Лазарян Всеволод Арутюнович / редкол. С. В. Мямлин, Е. П. Блохин, И. В. Клименко, В. В. Карпенко ; Днепропетр. нац. ун-т ж.-д. трансп. им. акад. В. Лазаряна. — Днепропетровск : ДНУЖТ, 2009. — 45 с. : портр. — (Серия "Профессора ДИИТа").RU: В настоящем издании приведены краткие сведения о жизни, научной и педагогической деятельности академика Лазаряна В. А., который 17 лет возглавлял институт и 34 года - кафедру строительной механики.UK: У цьому виданні наведені короткі відомості про життя, наукової та педагогічної діяльності академіка Лазаряна В. А., який 17 років очолював інститут і 34 роки - кафедру будівельної механіки.Днепропетровский национальный университет железнодорожного транспорта имени академика В. Лазарян

    Cultivation of Cells in a Physiological Plasmax Medium Increases Mitochondrial Respiratory Capacity and Reduces Replication Levels of RNA Viruses

    No full text
    Changes in metabolic pathways are often associated with the development of various pathologies including cancer, inflammatory diseases, obesity and metabolic syndrome. Identification of the particular metabolic events that are dysregulated may yield strategies for pharmacologic intervention. However, such studies are hampered by the use of classic cell media that do not reflect the metabolite composition that exists in blood plasma and which cause non-physiological adaptations in cultured cells. In recent years two groups presented media that aim to reflect the composition of human plasma, namely human plasma-like medium (HPLM) and Plasmax. Here we describe that, in four different mammalian cell lines, Plasmax enhances mitochondrial respiration. This is associated with the formation of vast mitochondrial networks and enhanced production of reactive oxygen species (ROS). Interestingly, cells cultivated in Plasmax displayed significantly less lysosomes than when any standard media were used. Finally, cells cultivated in Plasmax support replication of various RNA viruses, such as hepatitis C virus (HCV) influenza A virus (IAV), severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) and several others, albeit at lower levels and with delayed kinetics. In conclusion, studies of metabolism in the context of viral infections, especially those concerning mitochondria, lysosomes, or redox systems, should be performed in Plasmax medium
    corecore