•Chloroquine (CQ) has diverse modes of action against viral infections.•CQ may interfere with SARS-CoV-2 attachment to the host ACE2 receptor.•CQ may hamper the STING pathway to attenuate the ...pro-inflammatory response.•Hydroxychloroquine (HCQ) might be a logical approach in the treatment of SARS-CoV-2 infection.•Large clinical trials are needed before clinical recommendations of HCQ against COVID-19.
Chloroquine (CQ) and its analogue hydroxychloroquine (HCQ) have long been used worldwide as frontline drugs for the treatment and prophylaxis of human malaria. Since the first reported cases in Wuhan, China, in late December 2019, humans have been under threat from coronavirus disease 2019 (COVID-19) caused by the novel coronavirus SARS-CoV-2 (previously known as 2019-nCoV), subsequently declared a pandemic. While the world is searching for expedited approval for a vaccine, which may be only preventative and not a cure, physicians and country leaders are considering several concerted clinical trials suggesting that the age-old antimalarial drugs CQ/HCQ could be a potent therapeutic against COVID-19. Based on accumulating scientific reports, here we highlight the possible modes of action of CQ/HCQ that could justify its use against viral infections. Considering the global health crisis of the COVID-19 pandemic, the option of repurposing old drugs, e.g. CQ/HCQ, particularly HCQ, for the treatment of SARS-CoV-2 infection could be a good choice. CQ/HCQ has diverse modes of action, including alteration of the acidic environment inside lysosomes and late endosomes, preventing endocytosis, exosome release and phagolysosomal fusion, and inhibition of the host cytokine storm. One or more diverse mechanisms might work against viral infections and reduce mortality. As there is no cure for COVID-19, clinical testing of HCQ is urgently required to determine its potency against SARS-CoV-2, as this is the currently available treatment option. There remains a need to find other innovative drug candidates as possible candidates to enter clinical evaluation and testing.
All organisms, including unicellular pathogens, compulsorily possess DNA topoisomerases for successful nucleic acid metabolism. But particular subtypes of topoisomerases exist, in all prokaryotes and ...in some unicellular eukaryotes, that are absent in higher eukaryotes. Moreover, topoisomerases from pathogenic members of a niche possess some unique molecular architecture and functionalities completely distinct from their nonpathogenic colleagues. This review will highlight the unique attributes associated with the structures and functions of topoisomerases from the unicellular pathogens, with special reference to bacteria and protozoan parasites. It will also summarise the progress made in the domain pertaining to the druggability of these topoisomerases, upon which a future platform for therapeutic development can be successfully constructed.
Topoisomerases from pathogenic members of a niche possess significant structural and functional differences from their nonpathogenic colleagues.
Plasmodium and Toxoplasma, despite being apicomplexan parasites, differ from each other significantly in topoisomerase distribution, structure, and function.
Few pathogens compensate the absence of a particular topoisomerase subtype by amplifying another topoisomerase variant.
Kinetoplastid pathogens possess a ‘unique’ bi-subunit topoisomerase IB, completely distinct from all other type IB enzymes.
Particular subtypes of topoisomerases exclusively exist in prokaryotes and in some unicellular eukaryotes. The absence of these enzymes in higher eukaryotes, including human, adds a new dimension in drug development research.
Pathogens from diverse genera show a similar molecular trend in mutating their topoisomerase genes to attain resistance against topo-targeted compounds.
The growing need of antimicrobial agent for novel therapies against multi-drug resistant bacteria has drawn researchers to green nanotechnology. Especially, eco-friendly biosynthesis of silver ...nanoparticles (Ag NPs) has shown its interesting impact against bacterial infection in laboratory research. In this study, a simple method was developed to form Ag NPs at room temperature, bio-reduction of silver ions from silver nitrate salt by leaf extract from Ocimum gratissimum. The Ag NPs appear to be capped with plant proteins, but are otherwise highly crystalline and pure. The Ag NPs have a zeta potential of −15mV, a hydrodynamic diameter of 31nm with polydispersity index of 0.65, and dry sizes of 18±3nm and 16±2nm, based on scanning and transmission electron microscopy respectively. The minimum inhibitory concentration (MIC) of the Ag NPs against a multi-drug resistant Escherichia coli was 4μg/mL and the minimum bactericidal concentration (MBC) was 8μg/mL, while the MIC and MBC against a resistant strain of Staphylococcus aureus were slightly higher at 8μg/mL and 16μg/mL respectively. Further, the Ag NPs inhibited biofilm formation by both Escherichia coli and S. aureus at concentrations similar to the MIC for each strain. Treatment of E. coli and S. aureus with Ag NPs resulted in damage to the surface of the cells and the production of reactive oxygen species. Both mechanisms likely contribute to bacterial cell death. In summary, this new method appears promising for green biosynthesis of pure Ag NPs with potent antimicrobial activity.
This work comprises the shape- and facet-dependent catalytic efficacies of different morphologies of CeO2, namely, hexagonal, rectangular, and square. The formation of different shapes of CeO2 is ...controlled using polyvinyl pyrrolidone as a surfactant. The surface reactivity of formation of differently exposed CeO2 facets is thoroughly investigated using UV–visible, photoluminescence, Raman, and X-ray photoelectron spectroscopies. A correlation between the growth of a surface-reactive facet and the corresponding oxygen vacancies is also established. Considering the tremendous contamination, caused by the textile effluents, the present study articulates the facet-dependent photocatalytic activities of pristine CeO2 for complete degradation of methylene blue within 175 min. The observed degradation time deploying pristine CeO2 as a catalyst is the shortest to be reported in the literature to our best knowledge.
•Calcium-loaded SnO2 sensors have been fabricated for detection of low-ppm CO.•The sensors exhibited a lower detection limit of 1ppm CO in air.•Response time (10s) comparable or superior to ...commercial solid-state sensors.•High selectivity to CO and minimal cross-sensitivity to VOCs and hydrocarbons.•Minimal preconditioning time and appreciable long-term stability.
Solid state sensors with noble metal-loaded tin oxide as sensing elements are widely used for the detection of flammable and toxic gases and volatile organic compounds (VOCs). Apart from rendering high cost, incorporation of noble metals often increases the preconditioning time and introduces a drift in baseline properties of the sensors. Herein, we report on the development of stable and economically viable sensor modules for fast and efficient detection of carbon monoxide (CO) in air. The sensing layer comprises sonochemically synthesized calcium-loaded tin oxide (Ca-SnO2) nanocrystals, in which calcium primarily gets segregated at the SnO2 grain boundaries as calcium oxide (CaO) and thereby restricts the growth of SnO2 particles. Due to larger ionic radius of Ca2+ as compared to that of Sn4+, a minute quantity of calcium can be doped as well into the SnO2 lattice. The variation of calcium concentration in SnO2 has a prominent effect on the sensor performance, where 5wt% calcium loading shows the highest sensor response. The sensors exhibit a lower detection limit of 1ppm CO in air. The response time (10–12s) and recovery time (30–45s) of our sensors, for different concentrations of CO, are equivalent or less compared to those of commercially available metal-oxide sensors. Additionally, a highly stable baseline with minimal drift even after being operational for over 1.5 years is observed.
The phytochemicals present in the stem bark extract of
Nerium oleander
(commonly known as Karabi) have been utilized for the green synthesis of stable gold-conjugated nanoparticles at room ...temperature under very mild conditions. The green synthesized gold-conjugated nanoparticles were characterized by surface plasmon resonance spectroscopy, High resolution transmission electron microscopy, X-ray diffraction studies and dynamic light scattering. A mechanism for the synthesis and stabilization of gold-conjugated nanoparticles (AuNPs) has been proposed. Anticancer activity of the stabilized AuNPs studied against MCF-7 breast cancer cell line revealed that the stabilized AuNPs were highly effective for the apoptosis of cancer cells selectively. The antioxidant activity of the stem bark extract of
Nerium oleander
has also been studied against a long lived 2,2-diphenylpicrylhydrazyl radical at room temperature. Moreover, the utilization of the stabilized AuNPs as a catalyst has also been demonstrated.
Mesoporous CeO2 nanospheres with appreciably high surface area are prepared using reversed micelles by a water-in-oil microemulsion method. The structural morphology and semiconducting properties of ...the nanoparticles are thoroughly investigated using X-ray diffraction, field effect scanning electron microscopy, transmission electron microscopy, and UV–visible spectroscopic techniques. Even after high-temperature calcination, the morphological retention of the material is apparent by electron microscopy. The deployment of undoped CeO2 nanospheres for the detection of low-ppm CO yields superior performances in terms of sensitivity, response–recovery times, and selectivity compared to those of other sensors of the same genre. These CO sensors exhibit ∼ 52% sensitivity with a response time of only 13 s. The sensor parameters are analyzed as a function of both temperature and gas concentration. In addition to that on the cost-effective and scalable synthesis of CeO2 nanospheres, this article also reports on the fabrication of packaged CO sensors, which can be potentially utilized for industrial and environmental monitoring purposes.
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•CoO NPs not produce any toxic effects on normal cells at in vivo system.•CoO NPs induced ROS and pro-inflammatory cytokines.•CoO NPs increased the NADPH oxidase activity.•CoO NPs ...induced TNFα-p38 MAPK-caspase 8/3 in both in vitro and in vivo system.
The aim of this study was to find out the intracellular signaling transduction pathways involved in cobalt oxide nanoparticles (CoO NPs) mediated oxidative stress in vitro and in vivo system. Cobalt oxide nanoparticles released excess Co++ ions which could activated the NADPH oxidase and helps in generating the reactive oxygen species (ROS). Our results showed that CoO NPs elicited a significant (p<0.05) amount of ROS in lymphocytes. In vitro pretreatment with N-acetylene cystine had a protective role on lymphocytes death induced by CoO NPs. In vitro and in vivo results showed the elevated level of TNF-α after CoO NPs treatment. This TNF-α phosphorylated the p38 mitogen-activated protein kinase followed by activation of caspase 8 and caspase 3 which could induce cell death. This study showed that CoO NPs induced oxidative stress and activated the signaling pathway of TNF-α-caspase-8-p38-caspase-3 to primary immune cells. This study suggested that bare CoO NPs are a toxic for primary human immune cells that deals directly with human health. Surface modification or surface functionalization may open the gateway for further use of CoO NPs in different industrial use or in biomedical sciences.
Zinc oxide (ZnO) nanostructures with controlled morphology have been synthesized by a facile sonochemical method using cetyltrimethylammonium bromide (cationic surfactant) as a structure directing ...agent. The influence of surfactant concentration on the evolution of morphology, from starlet-like 3D structures to 2D flakes, has been systematically investigated. Room temperature formation of phase-pure ZnO crystals has been confirmed by X-ray diffraction (XRD). Field emission scanning electron microscopy (FESEM) reveals the dimensions of ZnO flakes, which are 200–400nm wide and a few nanometre thick. Molecular fingerprints of the synthesized materials have been obtained by Fourier transform infrared spectroscopy (FTIR), while UV–vis spectroscopy estimates the bandgap of ZnO as 3.37eV.
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•ZnO nanostructures were synthesized by a fast and facile sonochemical method.•The temperature was restricted to 27°C throughout the synthesis process.•Phase-pure ZnO nanostructures were obtained without the need for calcination.•Evolution of 3D starlets to 2D flakes or sheets occurred by varying surfactant concentration.
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Classical models illustrate the genesis of bottom-up techniques for synthesis of pristine ZnO or Al-doped ZnO nanoparticles via surfactant aided or hydrothermal chemistry, to ...constitute the fundamental modules of nanotechnology and nanodevices. The present study demonstrates a facile as well as surfactant and catalyst free route for synthesis of morphology controlled Al-doped ZnO nanorods. Morphological evaluation (via FESEM and TEM characterization) clearly verifies the successful synthesis of ZnO and Al-doped ZnO nanorods. Moreover, crystallographic and FTIR studies ratified presence of multiple different planes as well as phases of ZnO and Al-doped ZnO nanostructures, eventually confirming the doping process. Further, the alteration in mode of electronic transition and surface charge of ZnO nanorods post doping with Al was witnessed from its UV–visible or photoluminescence spectra and zeta potential measurements, respectively. Electrical measurements were performed on prepared Al-doped ZnO nanorods which were fabricated as single nanorod devices. Owing to substitutional and interstitial doping, the electrical conductivity of the devices was drastically enhanced after doping. Excellent electrical attribute of the nanorods when fabricated into single nanorod device was indicative of its potential to be deployed as next generation nano-biosensors or piezo-electric devices.
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