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Infectious diseases caused by viruses like HIV and SARS-COV-2 (COVID-19) pose serious public health threats. In search for new antiviral small molecules from chemically underexplored Hypericum species, a previously undescribed atropisomeric C8-C8’ linked dimeric coumarin named bichromonol (1) was isolated from the stem bark of Hypericum roeperianum. The structure was elucidated by MS data and NMR spectroscopy. The absolute configuration at the biaryl axis was determined by comparing the experimental ECD spectrum with those calculated for the respective atropisomers. Bichromonol was tested in cell-based assays for cytotoxicity against MT-4 (CC50 = 54 µM) cells and anti-HIV activity in infected MT-4 cells. It exhibits significant activity at EC50 = 6.6–12.0 µM against HIV-1 wild type and its clinically relevant mutant strains. Especially, against the resistant variants A17 and EFVR, bichromonol is more effective than the commercial drug nevirapine and might thus have potential to serve as a new anti-HIV lead.

Cost degression in photovoltaics, wind-power and battery storage has been faster than previously anticipated. In the future, climate policy to limit global warming to 1.5–2 °C will make carbon-based fuels increasingly scarce and expensive. Here we show that further progress in solar- and wind-power technology along with carbon pricing to reach the Paris Climate targets could make electricity cheaper than carbon-based fuels. In combination with demand-side innovation, for instance in e-mobility and heat pumps, this is likely to induce a fundamental transformation of energy systems towards a dominance of electricity-based end uses. In a 1.5 °C scenario with limited availability of bioenergy and carbon dioxide removal, electricity could account for 66% of final energy by mid-century, three times the current levels and substantially higher than in previous climate policy scenarios assessed by the Intergovernmental Panel on Climate Change. The lower production of bioenergy in our high-electrification scenarios markedly reduces energy-related land and water requirements. The impact of rapidly falling costs of renewable energy and battery technology on long-term climate stabilization pathways is not well understood. Luderer et al. show that reduced renewable costs and climate policies will make electricity the cheapest energy carrier and can lead to electricity accounting for nearly two-thirds of global energy use by mid-century.

Background: For the last thirty years, the benzotriazole scaffold has been the object of our group interest and we have already presented some results on the antiviral activity of our compounds. Objective: In this article, we conclude the exploration of N-(4-(R-2H-benzo[d][1,2,3]triazol-2-yl)phenyl)-4-R’-benzamides and 1-(4-(R-2H-benzo[d][1,2,3]triazol-2-yl)phenyl)-3-R’-ureas by synthesizing further modified derivatives, in order to have more elements for SARs evaluation. Methods: Here, we reported the synthesis and the antiviral screening results of 38 newly synthesized benzotriazole derivatives against a panel of DNA and RNA viruses. We also analyse SARs in comparing these compounds with previously published benzotriazole analogues, taking stock of the situation. Results: Among the newly presented derivatives, compounds 17 and 18 were the most active with EC50 6.9 and 5.5 µM, respectively against Coxsackievirus B5 (CV-B5) and 20.5 and 17.5 µM against Poliovirus (Sb-1). Conclusion: we can conclude that N-(4-(2H-benzo[d] [1 - 3] triazol-2-yl)phenyl-R-amide is a good chemical scaffold for the development of new antiviral molecules.

This paper presents the new and now open-source version 2.1 of the REgional Model of INvestments and Development (REMIND). REMIND, as an integrated assessment model (IAM), provides an integrated view of the global energy–economy–emissions system and explores self-consistent transformation pathways. It describes a broad range of possible futures and their relation to technical and socio-economic developments as well as policy choices. REMIND is a multiregional model incorporating the economy and a detailed representation of the energy sector implemented in the General Algebraic Modeling System (GAMS). It uses non-linear optimization to derive welfare-optimal regional transformation pathways of the energy-economic system subject to climate and sustainability constraints for the time horizon from 2005 to 2100. The resulting solution corresponds to the decentralized market outcome under the assumptions of perfect foresight of agents and internalization of external effects. REMIND enables the analyses of technology options and policy approaches for climate change mitigation with particular strength in representing the scale-up of new technologies, including renewables and their integration in power markets. The REMIND code is organized into modules that gather code relevant for specific topics. Interaction between different modules is made explicit via clearly defined sets of input and output variables. Each module can be represented by different realizations, enabling flexible configuration and extension. The spatial resolution of REMIND is flexible and depends on the resolution of the input data. Thus, the framework can be used for a variety of applications in a customized form, balancing requirements for detail and overall runtime and complexity.

The fusion between the viral and the target cell membrane is a crucial step in the life cycle of enveloped viruses. The blocking of this process is a well-known therapeutic approach that led to the development of the fusion inhibitor peptide enfuvirtide, clinically used against human immunodeficiency virus (HIV) type 1. Despite this significant advance on viral treatment, the appearance of resistance has limited its clinical use. Such a limitation has led to the development of other fusion inhibitor peptides, such as C34, that present the same structural domain as enfuvirtide (heptad repeat sequence) but have different functional domains (pocket-binding domain in the case of C34 and lipid-binding domain in the case of enfuvirtide). Recently, the antiviral properties of 25-hydroxycholesterol were demonstrated, which boosted the interest in this oxysterol. The combination of two distinct antiviral molecules, C34 and 25-hydroxycholesterol, may help to suppress the emergence of resistant viruses. In this work, we characterized the interaction of the C34-25-hydroxycholesterol conjugate with biomembrane model systems and human blood cells. Lipid vesicles and monolayers with defined lipid compositions were used as biomembrane model systems. The conjugate interacts preferentially with membranes rich in sphingomyelin (a lipid enriched in lipid rafts) and presents a poor partition to membranes composed solely of phosphatidylcholine and cholesterol. We hypothesize that cholesterol causes a repulsive effect that is overcome in the presence of sphingomyelin. Importantly, the peptide shows a preference for human peripheral blood mononuclear cells relative to erythrocytes, which shows its potential to target CD4 + cells. Antiviral activity results against different wild-type and drug-resistant HIV strains further demonstrated the potential of C34-HC as a good candidate for future studies. Fil: Gomes, Bárbara. Universidade Nova de Lisboa. Faculdade de Ciencias Medicas; Portugal Fil: Sanna, Giusepinna. University of Cagliary; Italia Fil: Madeddu, Silvia. University of Cagliary; Italia Fil: Hollmann, Axel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet Noa Sur. Centro de Investigación en Biofísica Aplicada y Alimentos. - Universidad Nacional de Santiago del Estero. Centro de Investigación en Biofísica Aplicada y Alimentos; Argentina. Universidad Nacional de Quilmes; Argentina Fil: Santos, Nuno C.. Universidade Nova de Lisboa. Faculdade de Ciencias Medicas; Portugal

Enterovirus A71 (EV-A71) infection has emerged as a significant public health concern atthe global level. Epidemic events of EV-A71 have been reported worldwide, and this succession of outbreaks has heightened concern that EV-A71 may become a public health threat. In recent years, widespread A71 enterovirus also occurred in European countries. EV-A71 infection causes hand-foot-mouth disease (HFMD), herpangina, and fever. However, it can sometimes induce a variety of neurological complications, including encephalitis, aseptic meningitis, pulmonary edema, and acute flaccid paralysis. We identified new benzimidazole derivatives and described their in vitro cytotoxicity and broad-spectrum anti-enterovirus activity. Among them, derivative 2b resulted in interesting activity against EV-A71, and therefore it was selected for further investigations. Compound 2b proved to be able to protect cell monolayers from EV-A71-induced cytopathogenicity, with an EC50 of 3 µM. Moreover, Vero-76 cells resulted in being significantly protected from necrosis and apoptosis when treated with 2b at 20 and 80 µM. Compound 2b reduced viral adsorption to Vero-76 cells, and when evaluated in a time-of-addition assay, the derivative had the highest effect when added during the infection period. Moreover, derivative 2b reduced viral penetration into host cells. Besides, 2b did not affect intestinal monolayers permeability, showing no toxic effects. A detailed insight into the efficacy of compound 2b against EV-A71 showed a dose-dependent reduction in the viral titer, also at low concentrations. Mechanism of action investigations suggested that our derivative can inhibit viral endocytosis by reducing viral attachment to and penetration into host cells. Pharmacokinetic and toxicity predictions validated compound 2b as a good candidate for further in vivo assays.

The genome sequences of 10 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains from Sliema, Malta, were obtained by Nanopore sequencing using the amplicon sequencing approach developed by the Artic Network. The assembled genomes were analyzed with Pangolin software and assigned to the B.1 lineage, which is widely circulating in Europe.

In the prevention of epidemic and pandemic emerging and neglected viral infections, natural products are an important source of lead compounds.

The rapid emergence of drug-resistant strains and novel viruses have motivated the search for new anti-infectious agents. In this study, the chemical compositions and cytotoxicity, as well as the antibacterial, antifungal, antitrichomonas, and antiviral activities of essential oils from the leaves, rhizomes, and whole plant of Hornstedtia bella were investigated. The GC/MS analysis showed that &beta, pinene, E-&beta, caryophyllene, and &alpha, humulene were found at high concentrations in the essential oils. The essential oils exhibited (i) inhibition against Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, Staphylococcus epidermidis with minimum inhibitory concentrations (MIC) and minimum lethal concentration (MLC) values from 1 to 4% (v/v), (ii) MIC and MLC values from 2 to 16% (v/v) in Candida tropicalis and Candida parapsilosis, (iii) MIC and MLC values from 4 to 16% in Enterococcus faecalis, and (iv) MIC and MLC values from 8 to greater than or equal to 16% (v/v) in the remaining strains, including Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Candida albicans, and Candida glabrata. In antitrichomonas activity, the leaves and whole-plant oils of Hornstedtia bella possessed IC50, IC90, and MLC values of 0.008%, 0.016%, and 0.03% (v/v), respectively, whilst those of rhizomes oil had in turn, 0.004%, 0.008%, and 0.016% (v/v).Besides, the leaf oil showed a weak cytotoxicity against Vero 76 and MRC-5, meanwhile, rhizomes and whole-plant oils did not exert any toxic effects on cell monolayers. Finally, these oils were not active against EV-A71.

In the prevention of epidemic and pandemic emerging and neglected viral infections, natural products are an important source of lead compounds. Hornstedtia bella Škorničkis is a rhizomatous herb growing in the forest of central Vietnam. Hornstedtia bella essential oil (Hb EO) was recently characterised by our group as endowed of antimicrobial activity against Staphylococcus aureus Methicillin-Resistant strains. Here, we describe for the first time the evaluation of Hb EO against a spectrum of viruses responsible for important human diseases. Hb EO resulted active against Vaccinia virus (VV) (EC50 values 80 μg/mL), closely related to variola virus, causative agent of smallpox. Hb EO was able to strongly reduce the viral VV titer in cell-based assay at not cytotoxic concentration and its potential mode of action was characterised by virucidal activity evaluation followed by time-of-addition assay. Furthermore, Hb EO antiviral activity was implemented in a combination study with the mycophenolic acid.

Thiourea derivatives have been reported to possess many biological activities, among them antiviral and antitumoral properties. As part of our continuing effort to develop new active compounds, we report the synthesis and the evaluation of new fifteen thiourea derivatives with 1,3-benzothiazole-2-yl moiety, among them a group of biologically active (1-7) also underwent cyclization to 1,3-thiazolidin-4-ones. Molecular structure of four compounds (4, 13, 15 and 3a) was determined by an X-ray crystallography. We here report the evaluation of their cytotoxicity against human leukaemia/lymphoma- and solid tumour-derived cell lines and of their antiviral activity against HIV-1 and representatives of ssRNA and dsDNA viruses. Derivative 5 showed an interesting activity against HIV-1 wild type and against variants carrying clinically relevant mutations. A colorimetric enzyme immunoassay clarified its mode of action as a non-nucleoside inhibitor of the reverse transcriptase.

Background: Coxsackievirus infections are associated with cases of aseptic meningitis, encephalitis, myocarditis, and some chronic disease. Methods: A series of benzo[d][1,2,3]triazol-1(2)-yl derivatives (here named benzotriazol-1(2)-yl) (4a-i, 5a-h, 6a-e, g, i, j and 7a-f, h-j) were designed, synthesized and in vitro evaluated for cytotoxicity and antiviral activity against two important human enteroviruses (HEVs) members of the Picornaviridae family [Coxsackievirus B 5 (CVB-5) and Poliovirus 1 (Sb-1)]. Results: Compounds 4c (CC50 >100 μM; EC50 = 9 μM), 5g (CC50 >100 μM; EC50 = 8 μM), and 6a (CC50 >100 μM; EC50 = 10 μM) were found active against CVB-5. With the aim of evaluating the selectivity of action of this class of compounds, a wide spectrum of RNA (positive- and negativesense), double-stranded (dsRNA) or DNA viruses were also assayed. For none of them, significant antiviral activity was determined. Conclusion: These results point towards a selective activity against CVB-5, an important human pathogen that causes both acute and chronic diseases in infants, young children, and immunocompromised patients.

A clinical isolate of measles virus (MeV) bearing a single amino acid alteration in the viral fusion protein (F; L454W) was previously identified in two patients with lethal sequelae of MeV central nervous system (CNS) infection. The mutation dysregulated the viral fusion machinery so that the mutated F protein mediated cell fusion in the absence of known MeV cellular receptors. While this virus could feasibly have arisen via intrahost evolution of the wild-type (wt) virus, it was recently shown that the same mutation emerged under the selective pressure of small-molecule antiviral treatment. Under these conditions, a potentially neuropathogenic variant emerged outside the CNS. While CNS adaptation of MeV was thought to generate viruses that are less fit for interhost spread, we show that two animal models can be readily infected with CNS-adapted MeV via the respiratory route. Despite bearing a fusion protein that is less stable at 37°C than the wt MeV F, this virus infects and replicates in cotton rat lung tissue more efficiently than the wt virus and is lethal in a suckling mouse model of MeV encephalitis even with a lower inoculum. Thus, either during lethal MeV CNS infection or during antiviral treatment in vitro, neuropathogenic MeV can emerge, can infect new hosts via the respiratory route, and is more pathogenic (at least in these animal models) than wt MeV. IMPORTANCE Measles virus (MeV) infection can be severe in immunocompromised individuals and lead to complications, including measles inclusion body encephalitis (MIBE). In some cases, MeV persistence and subacute sclerosing panencephalitis (SSPE) occur even in the face of an intact immune response. While they are relatively rare complications of MeV infection, MIBE and SSPE are lethal. This work addresses the hypothesis that despite a dysregulated viral fusion complex, central nervous system (CNS)-adapted measles virus can spread outside the CNS within an infected host.

Human Respiratory Syncytial Virus (RSV) is the primary cause of bronchopneumonia in infants and children worldwide. Clinical studies have shown that early treatments of RSV patients with ribavirin improve prognosis, even if the use of this drug is limited due to myelosuppression and toxicity effects. Furthermore, effective vaccines to prevent RSV infection are currently unavailable. Thus, the development of highly effective and specific antiviral drugs for pre-exposure prophylaxis and/or treatment of RSV infections is a compelling need. In the quest of new RSV inhibitors, in this work we evaluated the antiviral activity of a series of variously substituted 5,6-dichloro-1-phenyl-1(2)H-benzo[d][1,2,3]triazole derivatives in cell-based assays. Several 1- and 2-phenyl-benzotriazoles resulted fairly potent (µM concentrations) inhibitors of RSV infection in plaque reduction assays, accompanied by low cytotoxicity in human highly dividing T lymphoid-derived cells and primary cell lines. Contextually, no inhibitory effects were observed against other RNA or DNA viruses assayed, suggesting specific activity against RSV. Further results revealed that the lead compound 10d was active during the early phase of the RSV infection cycle. To understand whether 10d interfered with virus attachment to target cells or virus-cell fusion events, inhibitory activity tests against the RSV mutant strain B1 cp-52 – expressing only the F envelope glycoprotein – and a plasmid-based reporter assay that quantifies the bioactivity of viral entry were also performed. The overall biological results, in conjunction with in silico modeling studies, supported the conclusion that the RSV fusion process could be the target of this new series of compounds.

Nerium oleander (NO), a member of the Apocynaceae family, is an ornamental plant. In this study, we evaluated the antiviral activity of hot and cold extract of NO against six different viruses such as herpes simplex virus type 1 (HSV-1), polio virus type 1 (Sb-1), vesicular stomatitis virus (VSV), reovirus type-1 (Reo-1), human immunodeficiency virus type-1 (HIV-1), and yellow fever virus (YFV). Interestingly the results of plaque reduction assay demonstrated that both, hot extract and cold extract (breastin) of NO inhibited Sb-1 viral infection. In order to identify the mechanism by which NO exerts its antiviral activity, the virucidal effect, the time of addition and the adsorption assay were carried out. Results demonstrated that NO exerts its effect after infection period, particularly during the first two hours post infection.

Nucleoside analogues play an important role in antiviral, antibacterial and antineoplastic chemotherapy. Herein we report the synthesis, structural characterization and biological activity of some 4′-C -methyl- and -phenyl dioxolane-based nucleosides. In particular, α and β anomers of all natural nucleosides were obtained and characterized by NMR, HR-MS and X-ray crystallography. The compounds were tested for antimicrobial activity against some representative human pathogenic fungi, bacteria and viruses. Antitumor activity was evaluated in a large variety of human cancer cell-lines. Although most of the compounds showed non-significant activity, 23α weakly inhibited HIV-1 multiplication. Moreover, 22α and 32α demonstrated a residual antineoplastic activity, interestingly linked to the unnatural α configuration. These results may provide structural insights for the design of active antiviral and antitumor agents.

Historically, natural products have been the most successful source of inspiration for the development of new drugs. Members of the Thymelaeaceae family have been of interest owing to their excellent medicinal value. Given the successful history of natural product-based drug discovery, extracts from the aerial parts of Thymelaea hirsuta were essvaluated for their potential anti-human immunodeficiency virus type 1 (HIV-1) activity. Ethyl acetate extracts from leaves (71B) and branches (72B) of Thymelaea hirsuta showed potent and selective activity against HIV-1 wt (EC50 = 0.8 &micro, g/mL) at non-cytotoxic concentrations (CC50 &gt, 100 &micro, g/mL). They proved to be active against HIV-1 variants carrying clinically relevant NNRTI and NRTI mutations at low concentration (0.3&ndash, 4 &micro, g/mL range) and against the M-tropic strain HIV-1 BaL. The 72B extract, chosen as a lead, was not able to inhibit the RT and protease enzymatic functions. Furthermore, it was not virucidal, since exposure of HIV to high concentration did not affect virus infectivity. The pre-clinical safety profile of this extract showed no adverse effect on the growth of Lactobacilli, and non-toxic concentration of the extract did not influence the Caco-2 epithelial cells monolayer integrity. Additionally, extract 72B prevented syncytia formation at low concentration (0.4 &micro, g/mL). The potent inhibitory effect on the syncytia formation in co-cultures showed that 72B inhibits an early event in the replication cycle of HIV. All of these findings prompt us to carry on new studies on Thymelaea hirsuta extracts.

© 2019 Elsevier B.V. This manuscript presents the computational and experimental studies of a new thiourea derivative 1-(4-chloro-3-nitrophenyl)-3-(3,4-dichlorophenyl)thiourea (CNDCT). Scaled simulated and experimental IR and Raman spectra were compared and the vibrational modes are assigned to proper vibrations followed by potential energy distribution study. Weakening of N-H bond is observed from the red shift in NH stretching mode values from the theoretical wavenumber values. Natural bond orbital studies provide the stability of the molecule and predict the change properties upon the charge delocalization. Reactive sites in the molecule were identified using molecular electrostatic potential figures. According to QTAIM analysis, the locations of noncovalent interactions in CNDCT-1 and CNDCT-3 are practically the same. The difference in case of the CNDCT-2 is that noncovalent interaction is formed between atoms N7-H30, instead between atoms O20-C12. Average Local Ionization Energy (ALIE) and Fukui functions provide information about the exact atoms susceptible to various attacks. The tendency of the molecule to undergo air autoxidation was found from the bond dissociation energies (BDE) values and the interaction of the molecules with solvent system was analyzed using and radial distribution functions (RDF) obtained from molecular dynamics (MD) simulations. NLO studies indicate that the candidate molecule is a good NLO material compared to that of urea. Docking studies reveal that the title compound shows the inhibitory activity against Farnesoid X receptor.

Orthohantaviruses, previously known as hantaviruses (family Hantaviridae, order Bunyavirales), are emerging zoonoses hosted by different rodent and insectivore species. Orthohantaviruses are transmitted by aerosolized excreta (urine, saliva and feces) of their reservoir hosts. When transmitted to humans, they cause hemorrhagic fever with renal syndrome (HFRS) in Asia and Europe and hantavirus (cardio) pulmonary syndrome (HPS) in the Americas. Clinical studies have shown that early treatments of HFRS patients with ribavirin (RBV) improve prognosis. Nevertheless, there is the need for urgent development of specific antiviral drugs. In the search for new RNA virus inhibitors, we recently identified a series of variously substituted 5,6-dichloro-1(2)-phenyl-1(2)H-benzo[d][1,2,3]triazole derivatives active against the human respiratory syncytial virus (HRSV). Interestingly, several 2-phenyl-benzotriazoles resulted in fairly potent inhibitors of the Hantaan virus in a chemiluminescence focus reduction assay (C-FRA) showing an EC50 = 4−5 µM, ten-fold more active than ribavirin. Currently, there are no FDA approved drugs for the treatment of orthohantavirus infections. Antiviral activities and cytotoxicity profiles suggest that 5,6-dichloro-1(2)-phenyl-1(2)H-benzo[d][1,2,3]triazoles could be promising candidates for further investigation as a potential treatment of hantaviral diseases.

The high worldwide demand for amorphous precipitated silica (APS) materials, millions of tons worth billions of dollars, makes it worthwhile to further expand the techniques for synthesizing new, cheap, and environmentally friendly resources. In this research, amorphous precipitated silica was synthesized from alkaline dissolution of olivine using a mixture of NaOH and KOH and characterized; this combination resulted in better kinetics than those of the separate components. Experimental parameters (concentration of alkali, liquid/solid ratio, reaction time, and temperature) were optimized to provide maximum recovery of APS from olivine dissolution, which was then characterized using X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), Brunauer–Emmett–Teller (BET) N2 adsorption–desorption measurements, and thermogravimetric analysis (TGA). The APS possessed suitable morphology for use as an additive in polymers and in catalysis: a particle size below 10 nm, pore width of 5.59 nm, BJH adsorption cumulative pore volume of 0.96 cm3 g−1, BET surface area of 670.8 m2 g−1, and Langmuir surface area of 859.3 m2 g−1. The apparent activation energy of olivine dissolution with a mixture of NaOH/KOH was 43.6 kJ mol−1. The steps involved in creation of APS from olivine resulted in opportunities for carbon dioxide absorption, which could contribute to the production of valuable materials through decarbonation of exhaust gases.

A series of 2-(1H-indol-3-yl)ethylthiourea derivatives were prepared by condensation of 2-(1H-indol-3-yl)ethanamine with appropriate aryl/alkylisothiocyanates in anhydrous media. The structures of the newly synthesized compounds were confirmed by spectroscopic analysis and the molecular structures of 8 and 28 were confirmed by X-ray crystallography. All obtained compounds were tested for antimicrobial activity against Gram-positive cocci, Gram-negative rods and for antifungal activity. Microbiological evaluation was carried out over 20 standard strains and 30 hospital strains. Compound 6 showed significant inhibition against Gram-positive cocci and had inhibitory effect on the S. aureus topoisomerase IV decatenation activity and S. aureus DNA gyrase supercoiling activity. Compounds were tested for cytotoxicity and antiviral activity against a large panel of DNA and RNA viruses, including HIV-1 and other several important human pathogens. Interestingly, derivative 8 showed potent activity against HIV-1 wild type and variants bearing clinically relevant mutations. Newly synthesized tryptamine derivatives showed also a wide spectrum activity, proving to be active against positive- and negative-sense RNA viruses.

A total of 31 of thiourea derivatives was prepared reacting 3-(trifluoromethyl)aniline and commercial aliphatic and aromatic isothiocyanates. The yields varied from 35% to 82%. All compounds were evaluated in vitro for antimicrobial activity. Derivatives 3 , 5 , 6 , 9 , 15 , 24 and 27 showed the highest inhibition against Gram-positive cocci (standard and hospital strains). The observed MIC values were in the range of 0.25–16 μg/ml. Inhibitory activity of thioureas 5 and 15 against topoisomerase IV isolated from Staphylococcus aureus was studied. Products 5 and 15 effectively inhibited the formation of biofilms of methicillin-resistant and standard strains of Staphylococcus epidermidis . Moreover, all obtained thioureas were evaluated for cytotoxicity and antiviral activity against a large panel of DNA and RNA viruses. Compounds 5, 6 , 8–12 , 15 resulted cytotoxic against MT-4 cells (CC 50 ≤ 10 μM).

The utilisation of Mg(OH)2 to capture exhaust CO2 has been hindered by the limited availability of brucite, the Mg(OH)2 mineral in natural deposits. Our previous study demonstrated that Mg(OH)2 can be obtained from dunite, an ultramafic rock composed of Mg silicate minerals, in highly concentrated NaOH aqueous systems. However, the large quantity of NaOH consumed was considered an obstacle for the implementation of the technology. In the present study, Mg(OH)2 was extracted from dunite reacted in solid systems with NaOH assisted with H2O. The consumption of NaOH was reduced by 97% with respect to the NaOH aqueous systems, maintaining a comparable yield of Mg(OH)2 extraction, i.e. 64.8–66%. The capture of CO2 from a CO2–N2 gas mixture was tested at ambient conditions using a Mg(OH)2 aqueous slurry. Mg(OH)2 almost fully dissolved and reacted with dissolved CO2 by forming Mg(HCO3)2 which remained in equilibrium storing the CO2 in the aqueous solution. The CO2 balance of the process was assessed from the emissions derived from the power consumption for NaOH production and Mg(OH)2 extraction together with the CO2 captured by Mg(OH)2 derived from dunite. The process resulted as carbon neutral when dunite is reacted at 250 °C for durations of 1 and 3 hours and CO2 is captured as Mg(HCO3)2.

Enteroviruses are among the most common and important human pathogens for which there are no specific antiviral agents approved by the US Food and Drug Administration so far. Particularly, coxsackievirus infections have a worldwide distribution and can cause many important diseases. We here report the synthesis of new 14 quinoxaline derivatives and the evaluation of their cytotoxicity and antiviral activity against representatives of ssRNA, dsRNA and dsDNA viruses. Promisingly, three compounds showed a very potent and selective antiviral activity against coxsackievirus B5, with EC50 in the sub-micromolar range (0.3 - 0.06 μM). A combination of experimental techniques (i.e. virucidal activity, time of drug addition and adsorption assays) and in silico modeling studies were further performed, aiming to understand the mode of action of the most active, selective and not cytotoxic compound, the ethyl 4-[(2,3-dimethoxyquinoxalin-6-yl)methylthio]benzoate (6).

On the basis of recently reported biologically active 3-(trifluoromethyl)phenylthioureas, a series of diaryl derivatives incorporating 1 H -tetrazol-5-yl ( 1a–11a , 1a’–11a’ ) and 1,3-thiazolidin-4-one ( 1b–11b ) scaffolds were synthesized. The synthesis pathway was confirmed by an X-ray crystallographic studies of 3a’ , 6a , 8a , 6b and 8b . The cytotoxicity against MT-4 cells and anti-HIV properties of new derivatives were evaluated. As compared to initial thiourea connections, the cyclisation reduced the cytotoxicity of compounds by 2–15 times. The most promising N-(4-nitrophenyl)-1 H -tetrazol-5-amine 7a was found to be more active than the origin thiourea. Its cytotoxicity was evaluated on A549, HTB-140 and HaCaT cell lines using MTT assay. The compound shows significant influence on cancer, but not on normal cells. Obtained results can provide some constructive data for further designing of novel family of potentially bioactive analogs.

© The Author(s) 2017. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/, Human paramyxoviruses include global causes of lower respiratory disease like the parainfluenza viruses, as well as agents of lethal encephalitis like Nipah virus. Infection is initiated by viral glycoprotein-mediated fusion between viral and host cell membranes. Paramyxovirus viral fusion proteins (F) insert into the target cell membrane, and form a transient intermediate that pulls the viral and cell membranes together as two heptad-repeat regions refold to form a six-helix bundle structure that can be specifically targeted by fusion-inhibitory peptides. Antiviral potency can be improved by sequence modification and lipid conjugation, and by adding linkers between the protein and lipid components. We exploit the uniquely broad spectrum antiviral activity of a parainfluenza F-derived peptide sequence that inhibits both parainfluenza and Nipah viruses, to investigate the influence of peptide orientation and intervening linker length on the peptides' interaction with transitional states of F, solubility, membrane insertion kinetics, and protease sensitivity. We assessed the impact of these features on biodistribution and antiviral efficacy in vitro and in vivo. The engineering approach based on biophysical parameters resulted in a peptide that is a highly effective inhibitor of both paramyxoviruses and a set of criteria to be used for engineering broad spectrum antivirals for emerging paramyxoviruses., This research was funded by NIH grants RO1AI114736, R33AI101333, and RO1AI031971 to A.M. and by ANRASTRID-2011. M.T.A. has fellowship support SFRH/BD/95624/2013 from Fundação para a Ciência e Tecnologia - Ministério da Educação e Ciência (FCT-MEC, Portugal) and support from Fundação Luso Americana para o Desenvolvimento (FLAD) Proj. 4/2016. We thank Peter Collins and Alex Bukreyev (National Institutes for Allergy and Infectious Diseases, National Institutes of Health, USA) for the recombinant HPIV3 expressing enhanced GFP.

Correction for ‘Synthesis and characterization of amorphous precipitated silica from alkaline dissolution of olivine’ by Nadeem Raza et al., RSC Adv., 2018, 8, 32651–32658.

The biological diversity of nature is the source of a wide range of bioactive molecules. The natural products, either as pure compounds or as standardized plant extracts, have been a successful source of inspiration for the development of new drugs. The present work was carried out to investigate the cytotoxicity, antiviral and antimycobacterial activity of the methanol extract and of four identified limonoids from the fruits of Melia azedarach (Meliaceae). The extract and purified limonoids were tested in cell-based assays for antiviral activity against representatives of ssRNA, dsRNA and dsDNA viruses and against Mycobacterium tuberculosis. Very interestingly, 3-α-tigloyl-melianol and melianone showed a potent antiviral activity (EC50 in the range of 3–11μM) against three important human pathogens, belonging to Flaviviridae family, West Nile virus, Dengue virus and Yellow Fever virus. Mode of action studies demonstrated that title compounds were inhibitors of West Nile virus only when added during the infection, acting as inhibitors of the entry or of a very early event of life cycle. Furthermore, 3-α-tigloyl-melianol and methyl kulonate showed interesting antimycobacterial activity (with MIC values of 29 and 70 μM respectively). The limonoids are typically lipophilic compounds present in the fruits of Melia azeradach. They are known as cytotoxic compounds against different cancer cell lines, while their potential as antiviral and antibacterial was poorly investigated. Our studies show that they may serve as a good starting point for the development of novel drugs for the treatment of infections by Flaviviruses and Mycobacterium tuberculosis, for which there is a continued need.

A series of new thiourea derivatives of 1,3-thiazole have been synthesized. All obtained compounds were tested in vitro against a number of microorganisms, including Gram-positive cocci, Gram-negative rods and Candida albicans. Compounds were also tested for their in vitro tuberculostatic activity against the Mycobacterium tuberculosis H37Rv strain, as well as two 'wild' strains isolated from tuberculosis patients. Compounds 3 and 9 showed significant inhibition against Gram-positive cocci (standard strains and hospital strain). The range of MIC values is 2-32 µg/mL. Products 3 and 9 effectively inhibited the biofilm formation of both methicillin-resistant and standard strains of S. epidermidis. The halogen atom, especially at the 3rd position of the phenyl group, is significantly important for this antimicrobial activity. Moreover, all obtained compounds resulted in cytotoxicity and antiviral activity on a large set of DNA and RNA viruses, including Human Immunodeficiency Virus type 1 (HIV-1) and other several important human pathogens. Compound 4 showed activity against HIV-1 and Coxsackievirus type B5. Seven compounds resulted in cytotoxicity against MT-4 cells (CC50

A set of 21 thiourea derivatives were prepared through reacting 3-amino-1H-1,2,4-triazole with the commercial aliphatic and aromatic isothiocyanates. The aliphatic isothiocyanate was used as reagent leading to substitution on NH atom of 3-aminotriazole ring, whereas the triazole amino group was substituted when isothiocyanate group was bonded to the Csp2 hybridized atom, e.g. an aryl or C=O fragment. All compounds were evaluated in vitro for the antimicrobial activity. The derivatives 1, 2, 4, 8, 9, 10 and 12 showed the highest inhibition against Gram-positive cocci (S. aureus and S. epidermidis). The observed MIC values were in the range of 4-32 μg/mL. Compounds were also tested for their in vitro antimicrobial activity against the hospital methicillin-resistant strains of S. aureus. The observed MIC values varied from 4 to 64 μg/mL. The products 4 and 10 effectively inhibited the formation of biofilms of the methicillin-resistant and standard strains of S. epidermidis. The compound 10 was found to be more promising with IC50 values of 2-6 μg/mL as compared to the control. Moreover, the cytotoxicity against the MT-4 cells of all studied thioureas was evaluated. The compound 18 was significantly cytotoxic (CC50 = 8 μM).