The emergence and rapid worldwide spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has prompted the scientific community to rapidly develop in vitro and in vivo models that could be applied in COVID-19 research. In vitro models include two-dimensional (2D) cultures of immortalized cell lines or primary cells and three-dimensional (3D) cultures derived from lung, alveoli, bronchi, and other organs. Although cell-based systems are economic and allow strict control of experimental variables, they do not always resemble physiological conditions. Thus, several in vivo models are being developed, including different strains of mice, hamsters, ferrets, dogs, cats, and non-human primates. In this review, we summarize the main models of SARS-CoV-2 infection developed so far and discuss their advantages, drawbacks and main uses.
O‐Acylamidoxime and 1,2,4‐oxadiazole derivatives were synthesized from adamantanecarbonyl chloride 1 and a diversity of arylamidoximes 2 a‐k. First, O‐acylamidoximes intermediates 3 a‐k were synthesized and subsequent cyclization under microwave irradiation afforded 1,2,4‐oxadiazol derivatives 4 a‐k. Molar Heat of Reaction Calorimetry studies performed from O‐acylamidoximes revealed influence of the substituent groups. A one‐pot two‐step methodology was also developed proving to be a viable protocol. Compounds were characterized by 1H and 13C Nuclear Magnetic Resonance (NMR) Spectroscopy, Elemental Analysis or High Resolution Mass Spectral Analysis, and subjected to cytotoxic studies in non‐tumoral Vero cells and antiproliferative activity tests in six malignant cell lines. Our findings suggest that compounds 3 derivatives presented a concentration‐dependent profile for chronic myeloid leukemia (K562) and acute promyelocytic leukemia (HL‐60) cell.
The appearance and spread of parasitic diseases around the world aroused the interest of the scientific community to discover new animal models for improving the quality and specificity of surveys. Calomys callosus is a rodent native to South America, an easy handling model, with satisfactory longevity and reproducibility. C. callosus is susceptible to toxoplasmosis and can be used as experimental model for the study the pathogenesis, treatment, vertical transmission, and ocular toxoplasmosis. C. callosus can also be used to study cutaneous and visceral leishmaniasis, as the animals present cutaneous lesions, as well as parasites in the organs. C. callosus has epidemiological importance in Chagas disease, and since it is a Trypanosoma cruzi natural host in which rodents show high parasitemia and lethality, they are also effective as a model of congenital transmission. In the study of schistosomiasis, Schistosoma mansoni was proven to be a C. callosus natural host; thus, this rodent is a great model for fibrosis, hepatic granulomatous reaction, and celloma associated with lymphomyeloid tissue (CALT) during S. mansoni infection. In this review, we summarize the leading studies of parasitic diseases that used C. callosus as a rodent experimental model, describing the main uses and characteristics that led them to be considered an effective model.
Two strategies were considered for the synthesis of 2,3-unsaturated O-glucosyl-1,2,3-triazoles. The first, involving reaction between triO -acetyl-D-glucal and triazole alcohols gave no stereoselectivity. A second strategy provided 2,3-unsaturated O-glycosides from glycals and alkynols through a Ferrier rearrangement; this method, employing montmorillonite K-10 doped with iron(III) chloride hexahydrate in dichloromethane afforded new glycosides in good to excellent yields within short times and with high α-stereoselectivities. Subsequently, the glucosides were coupled with 2-azido-1,4-naphthoquinone to produce a new series of 1,2,3-1H-triazolyl O-glucoside derivatives through a click reaction.
Zika virus (ZIKV) is an emerging arbovirus associated with neurological disorders. Currently, no specific vaccines or antivirals are available to treat the ZIKV infection. Ouabain, a cardiotonic steroid known as Na+/K+-ATPase inhibitor, has been previously described as an immunomodulatory substance by our group. Here, we evaluated for the first time the antiviral activity of this promising substance against a Brazilian ZIKV strain. Vero cells were treated with different concentrations of ouabain before and after the infection with ZIKV. The antiviral effect was evaluated by the TCID50 method and RT-qPCR. Ouabain presented a dose-dependent inhibitory effect against ZIKV, mainly when added post infection. The reduction of infectious virus was accompanied by a decrease in ZIKV RNA levels, suggesting that the mechanism of ZIKV inhibition by ouabain occurred at the replication step. In addition, our in silico data demonstrated a conformational stability and favorable binding free energy of ouabain in the biding sites of the NS5-RdRp and NS3-helicase proteins, which could be related to its mechanism of action. Taken together, these data demonstrate the antiviral activity of ouabain against a Brazilian ZIKV strain and evidence the potential of cardiotonic steroids as promising antiviral agents.
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