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1.
Vet Rec ; 190(1): 14, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34994424
2.
Ecotoxicol Environ Saf ; 229: 113097, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34942422

RESUMO

Chemical pesticides and adjuvants have caused many negative effects. Botanical compounds provide solutions for the development of environment friendly pesticides and the management of increasing pest resistance. Curcumin, a natural polyphenol, showed synergistic effects on avermectin upon the destructive agricultural pest, Spodoptera litura. However, the botanical synergist and its relevant mechanisms remain unclear. In the article, curcumin significantly enhanced the growth inhibition and midgut structural damage of avermectin on the larvae of S. litura, and the synergistic effects were confirmed with pot experiments. There were only a few influences on the gene expression of avermectin targets, while apoptotic and autophagic related genes and proteins were accumulated in the avermectin/curcumin mixed regent (0.013/0.0013 µg/mL) treated group. Moreover, the potential mechanism was explored with an in vitro model, insect Spodoptera frugiperda Sf9 cell line. Morphology observation featured the damage on cells and Hoechst33258 staining revealed the fragments of DNA after treating with the avermectin/curcumin mixed regent (10/1 µg/mL). Dansylcadaverine and LysoTracker staining, as well as the gene expressions, supposed that curcumin exhibited autophagy inducing effects and the mixed regent possessed a higher ability to induce apoptosis and autophagy. All these results suggested that the synergistic effects of curcumin on the pest management of avermectin potentially mainly derived from the enhancement of programed cell death. It provides new sights for the application of natural compounds in integrated pest management and enriches examples of synergistic mechanisms.


Assuntos
Curcumina , Animais , Apoptose , Curcumina/farmacologia , Ivermectina/análogos & derivados , Ivermectina/toxicidade , Larva , Spodoptera
3.
Chemosphere ; 286(Pt 1): 131030, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34144808

RESUMO

In current times of global change, several sources of stress such as contaminants and high temperatures may act synergistically. The extent to which organisms persist in stressful conditions will depend on the fitness consequences of multiple simultaneously acting stressors and the genetic basis of compensatory genetic responses. Ivermectin is an antiparasitic drug used in livestock that is excreted in dung of treated cattle, causing severe negative consequences on non-target fauna. We evaluated the effect of a combination of heat stress and exposure to ivermectin in the yellow dung fly, Scathophaga stercoraria (Diptera: Scathophagidae). In a first experiment we investigated the effects of high rearing temperature on susceptibility to ivermectin, and in a second experiment we assayed flies from a latitudinal gradient to assess potential effects of local thermal adaptation on ivermectin sensitivity. The combination of heat and ivermectin synergistically reduced offspring survival, revealing severe effects of the two stressors when combined. However, latitudinal populations did not systematically vary in how ivermectin affected offspring survival, body size, development time, cold and heat tolerance. We also found very low narrow-sense heritability of ivermectin sensitivity, suggesting evolutionary constraints for responses to the combination of these stressors beyond immediate maternal or plastic effects. If the revealed patterns hold also for other invertebrates, the combination of increasing climate warming and ivermectin stress may thus have severe consequences for biodiversity. More generally, our study underlines the need for quantitative genetic analyses in understanding wildlife responses to interacting stressors that act synergistically and threat biodiversity.


Assuntos
Dípteros , Ivermectina , Animais , Antiparasitários , Bovinos , Fezes , Resposta ao Choque Térmico , Ivermectina/toxicidade
4.
Colloids Surf B Biointerfaces ; 209(Pt 1): 112166, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34739877

RESUMO

To reduce the negative impact of nanopesticide carriers of on the environment, a greener nanodelivery system is necessary. Nanogels are nontoxic and degradable carriers, however, the potential of nanogels for delivering pesticides has not been proven. In this study, poly(vinyl alcohol)-valine, an ecofriendly polymer, was synthesized and used to fabricate emamectin benzoate nanogel suspension (EB NS). The nanoformulation showed favorable stability at low temperature, high temperature or one year storage, and in water with different hardnesses. The retention of the EB NS solution on leaves was higher than that of an EB emulsifiable concentrate (EC) by approximately 9% at a concentration of 10 mg L-1. The half-life of EB nanogels under Ultra Violet irradiation was prolonged by 3.3-fold. Moreover, the bioactivity of the EB NS against Plutella xylostella was higher than that of the EB EC. These advantages resulted in a relatively long duration of pest control. The response of nanogels to laccase, a digestive enzyme in the digestive tract of lepidopteran pests, enables pesticide release on demand. Nanogels have the advantages of being ecofriendly carriers, exhibiting higher utilization, and prolonged pest control periods, and they have a brilliant future in pesticide delivery.


Assuntos
Inseticidas , Álcool de Polivinil , Ivermectina/análogos & derivados , Lignina/análogos & derivados , Nanogéis , Polietilenoglicóis , Polietilenoimina , Valina
6.
Vet Parasitol ; 301: 109639, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34959085

RESUMO

Parasitic respiratory infections in domestic sheep and goats are caused by Dictyocaulus filaria and various species belonging to the Protostrongylidae family of nematodes which frequently occur in mixed infections. Although the parasitism with protostrongylid lungworms is generally considered to be of low pathogenicity, there are reports of clinical disease including cases associated with Protostrongylus rufescens infection. The efficacy against P. rufescens of eprinomectin 5 mg/mL topical solution (EPRINEX® Multi, Boehringer Ingelheim) was thus evaluated in a clinical study compliant with GCP and VICH anthelmintic efficacy testing guidelines in adult sheep with naturally acquired infection. Following ranking on pre-treatment Protostrongylus fecal larval counts and forming into blocks of two animals, the sheep were randomly allocated to either remain untreated (control) or to be administered eprinomectin 5 mg/mL topical solution at 1 mL/5 kg body weight (equivalent to 1 mg eprinomectin per kg body weight) once as a pour-on. Fecal samples of the sheep were examined to monitor the larval excretion weekly for five weeks after treatment; then the animals were necropsied for lungworm recovery and count to determine the efficacy of the treatment. After treatment, Protostrongylus larval excretion decreased to zero within three weeks. Nematode counts demonstrated that the efficacy of the treatment with eprinomectin 5 mg/mL topical solution was 100 % against P. rufescens: no lungworms were recovered from any treated sheep while all controls harbored P. rufescens (range, 17-406) (p < 0.001). The treatment was well accepted; no treatment-related health problems were observed.


Assuntos
Anti-Helmínticos , Doenças das Cabras , Metastrongyloidea , Infecções por Nematoides , Animais , Anti-Helmínticos/uso terapêutico , Doenças das Cabras/tratamento farmacológico , Ivermectina/análogos & derivados , Ivermectina/uso terapêutico , Infecções por Nematoides/tratamento farmacológico , Infecções por Nematoides/veterinária , Ovinos
7.
Parasitol Int ; 86: 102481, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34688883

RESUMO

Dirofilariasis is an emerging zoonosis caused by nematodes of the genus Dirofilaria, most often D. repens and D. immitis. The main final hosts and reservoirs of pathogens are dogs. The intermediate hosts and vectors of infection are female mosquitoes (Culicidae). Human is an accidental host in which the parasite does not usually mature. Over the past 20 years, the range of Dirofilaria spp. in Europe has expanded. We present an unusual case of multifocal dirofilariasis of mixed subcutaneous-ocular course caused by D. repens in a 52-year-old Polish patient who was probably infected in Spain or Croatia, where she stayed one year before the onset of symptoms. Surgical removal of the nematodes followed by treatment with Ivermectin in a single dose of 1200 µg and Doxycycline 200 mg daily for 7 days resulted in complete recovery. We believe that all cases of human dirofilariasis, especially in countries where the disease is not frequent at present, should be registered for epidemiological purposes. Moreover, due to the widening of the range of D. repens and D. immitis occurrence and the possibility of atypical courses of infection with both nematodes, diagnostics should include the species identification of the parasite.


Assuntos
Dirofilaria repens/isolamento & purificação , Dirofilariose/diagnóstico , Oftalmopatias/diagnóstico , Dermatopatias/diagnóstico , Animais , Antiparasitários/administração & dosagem , Croácia , Dirofilariose/tratamento farmacológico , Dirofilariose/parasitologia , Dirofilariose/cirurgia , Doxiciclina/administração & dosagem , Oftalmopatias/tratamento farmacológico , Oftalmopatias/parasitologia , Oftalmopatias/cirurgia , Feminino , Humanos , Ivermectina/administração & dosagem , Pessoa de Meia-Idade , Polônia , Dermatopatias/tratamento farmacológico , Dermatopatias/parasitologia , Dermatopatias/cirurgia , Espanha , Viagem , Resultado do Tratamento
8.
Acta Trop ; 225: 106218, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34755644

RESUMO

Community-Directed Treatment with Ivermectin (CDTI) is the strategy of choice to fight onchocerciasis in Africa. In areas where loiasis is endemic, onchocerciasis control and/or elimination is hindered by severe adverse events (SAEs) occurring after ivermectin mass treatments. This study aimed at (i) investigating the impact of two decades of CDTI on L. loa clinical and parasitological indicators in the Ndikinimeki Health District, and (ii) assessing the risk of SAEs after this long-term preventive chemotherapy. A cluster-based cross-sectional survey was conducted in the six Health Areas of the Ndikinimeki Health District. All volunteers underwent day-time calibrated thick blood smears to search for L. loa microfilariae, as well as an interview to assess the history of migration of eye worm and Calabar swelling. The overall prevalence of L. loa microfilaraemia was 2.2 % (95% CI: 1.3-3.7%), and the proportions of individuals who had already experienced eye worm and/or Calabar swelling were 1.0% and 0.5%, respectively. The mean microfilarial density was 63.55 (SD: 559.17; maximum: 9220.0) mf/mL. These findings indicate that (i) the long-term ivermectin-based preventive chemotherapy against onchocerciasis significantly reduced L. loa clinical and parasitological indicators, and (ii) the risk of developing neurologic and potentially fatal SAE after ivermectin mass treatment is zero in the Ndikinimeki Health District.


Assuntos
Loíase , Oncocercose , Animais , Camarões/epidemiologia , Estudos Transversais , Doenças Endêmicas/prevenção & controle , Humanos , Ivermectina , Loa , Loíase/tratamento farmacológico , Loíase/epidemiologia , Loíase/prevenção & controle , Oncocercose/tratamento farmacológico , Oncocercose/epidemiologia , Oncocercose/prevenção & controle , Prevalência
9.
Bol. micol. (Valparaiso En linea) ; 36(2): 20-31, dic. 2021. ilus
Artigo em Espanhol | LILACS | ID: biblio-1352757

RESUMO

En esta revisión de la literatura se describen aspectos epidemiológicos, fisiopatológicos, clínicos y terapéuticos sobre una presentación atípica y grave de escabiosis, la sarna costrosa o noruega. Esta presentación de escabiosis destaca por afectar principalmente a personas con condiciones de inmunodepresión o sociales que las hacen susceptibles de una alta carga parasitaria, además se asocia a un peor pronóstico y a riesgo de complicaciones. Desde el punto de vista terapéutico, sus estrategias difieren del manejo de la escabiosis clásica.(AU)


This literature review describes epidemiological, pathophysiological, clinical and therapeutic aspects of an atypical and severe presentation of scabies, Norwegian or crusty scabies. This presentation of scabies stands out because it mainly affects people with immunosuppressive or social conditions that make them susceptibleto a high parasite load, it is also associated with a worse prognosis and risk of complications. From a therapeutic point of view, their strategies differ from the management of classic scabies.(AU)


Assuntos
Humanos , Escabiose/fisiopatologia , Ectoparasitoses/etiologia , Sistema Imunitário/patologia , Sarcoptes scabiei/patogenicidade , Escabiose/diagnóstico , Escabiose/tratamento farmacológico , Ivermectina/administração & dosagem , Higiene
10.
J Agric Food Chem ; 69(51): 15530-15537, 2021 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-34914386

RESUMO

Naturally occurring avermectins are allosteric modulators of glutamate-gated chloride channels (GluCls) and possess exceptionally potent anthelmintic, acaricidal, and insecticidal activities. Here, we develop photoswitchable azobenzene-avermectin (ABAVM) derivatives, which can be photoactivated upon ultraviolet irradiation. After illumination, the best compound p-AB4″AVM had a 1.88-fold and 2.74-fold insecticidal activity enhancement toward Culex pipiens pallens and Mythimna separata larvae, respectively. p-AB4″AVM allows for optical regulation of dorsal unpaired median neuron membrane potential with a 2.15-fold fluorescence intensity decrease after illumination. p-AB4″AVM and p-AB5AVM enable optical modulation of the behavioral response of Culex pipiens pallens larvae with 1- and 4-fold reduced mobility upon irradiation, respectively. The ABAVMs could be used to reversibly manipulate GluCls with light and may be useful for the mechanistic study of macrocyclic lactone insecticides.


Assuntos
Culex , Inseticidas , Mariposas , Animais , Compostos Azo , Insetos , Inseticidas/farmacologia , Ivermectina/análogos & derivados , Larva
11.
S Afr Med J ; 111(10): 934-937, 2021 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-34949284

RESUMO

Some clinicians prescribe ivermectin for COVID-19 despite a lack of support from any credible South African professional body. They argue that when faced by clinical urgency, weak signals of efficacy should trigger action if harm is unlikely. Several recent reviews found an apparent mortality benefit by including studies at high risk of bias and with active rather than placebo controls. If these studies are discounted, the pooled mortality effect is no longer statistically significant, and evidence of benefit is very weak. Relying on this evidence could cause clinical harm if used to justify vaccine hesitancy. Clinicians remain responsible for ensuring that guidance they follow is both legitimate and reliable. In the ivermectin debate, evidence-based medicine (EBM) principles have largely been ignored under the guise thatin a pandemic the 'rules are different', probably to the detriment of vulnerable patients and certainly to the detriment of the profession's image. Medical schools and professional interest groups are responsible for transforming EBM from a taught but seldom-used tool into a process of lifelong learning, promoting a consistent call for evidence-based and unconflicted debate integral to clinical practice.


Assuntos
COVID-19/tratamento farmacológico , Ivermectina/administração & dosagem , Padrões de Prática Médica/normas , /psicologia , Vacinas contra COVID-19/administração & dosagem , Medicina Baseada em Evidências/normas , Humanos , Ivermectina/efeitos adversos , Projetos de Pesquisa , África do Sul
12.
Int J Pharm Compd ; 25(6): 523-527, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34807848

RESUMO

Ivermectin is a gamma amino butyric acid (GABA)-gated-Cl-channels modulator, which has been used orally in the treatment of numerous parasitic infections. The study target was to set up a stable, efficient 0.2% w/v ivermectin solution, which would be achieved from pure ivermectin powder as a source of the active pharmaceutical ingredient. Several trial solutions were prepared. The most fitting solution, with respect to its organoleptic properties, was chosen for additional investigation, including the solution's physical stability. Two storage conditions, room temperature (25°C, 60% relative humidity) and accelerated stability chambers (40°C, 75% relative humidity) were subjected to guarantee the physical stability of the solution through the 3-month study period. Furthermore, other quality tests were assessed, (e.g., pH, assay, organoleptic properties, microbial contamination) for the same latter period. Quantification of ivermectin was validated utilizing a high-performance liquid chromatography analytical method. The adopted solution showed accepted organoleptic properties. The pH of the solutions was approximately 5 and remained unchanged during the stability study. The mean percent of remained ivermectin solution was close to 97% ± 0.2 at room temperature. Ivermectin solution was additionally tested for microbial contamination, and it was free from any microbial contamination (E. coli bacteria: Negative/mL, yeast and molds count: <10 cfu/mL and aerobic microbial count results in <10 cfu/mL). The adopted formula showed the best physical stability within at least the three months of storage at both room and accelerated conditions. Ivermectin solution was successfully prepared from its pure powder. This formula provides a stable, efficient oral solution for those who suffer from swallowing difficulties or patients in the intensive care unit who cannot receive the medication in a solid dosage form. Using the suggested formula, community and hospital pharmacists could prepare an effective, high quality ivermectin oral solution using pure ivermectin powder.


Assuntos
Escherichia coli , Ivermectina , Cromatografia Líquida de Alta Pressão , Estabilidade de Medicamentos , Humanos , Resultado do Tratamento
13.
Exp Appl Acarol ; 85(2-4): 355-377, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34766246

RESUMO

The resistance status against deltamethrin, cypermethrin, coumaphos and ivermectin was assessed of Rhipicephalus microplus from five districts of Uttarakhand, through adult immersion test and larval packet test. The field isolates were highly resistant to deltamethrin (median resistance ratio [RR50] = 9.10-29.13-fold) followed by cypermethrin (2.23-3.55). Surprisingly the isolates were susceptible to coumaphos (0.34-3.17). Emerging resistance against ivermectin (1.55-3.27) was also observed in all the isolates. Elevated levels of esterases (enzyme ratio = 2.93-5.84-fold), glutathione S-transferases (5.10-10.06) and monooxygenases (1.68-4.02) in resistant fields isolates were highly correlated (47.4-86.0%) with the resistant factor (RR50) determined by bioassay. All the isolates except Uttarkashi possess mutation at the 190th position in domain II of the sodium channel gene. As a mitigation strategy an Ageratum conyzoides-based characterized natural formulation was tested against all the isolates and was found effective at the concentration of 10.1-11.5%. The possibility of using the natural formulation for the management of multi-acaricide resistant ticks is discussed.


Assuntos
Acaricidas , Piretrinas , Rhipicephalus , Animais , Cumafos , Índia , Ivermectina , Larva
14.
J Assoc Physicians India ; 69(11): 11-12, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34781604

RESUMO

BACKGROUND: Chemoprophylaxis (CP) along with masking and physical distancing seem an undeniable alternative. Considering the significant but uncertain role of CP for the current COVID-19 pandemic situation, we aimed to determine the various aspects of CP prescribing practices among physicians across India. METHODS: An online survey was conducted among prescribing physicians across India where physicians were assessed for their prescribing practices on COVID-19 CP. Responses to the questionnaire were obtained via telephone, email and WhatsApp messages. Responses were duly analyzed thereafter. RESULT: Ivermectin was the preffered choice in 44% individuals followed by hydroxychloroquine in 34% individuals. Odds of COVID contact among those using HCQ and / or IVR prophylaxis was less than 1 of which IVR was found more protective. The present study also made a survey among 309 community dwellers, where odds of contacted COVID among those with any prophylaxis was 0.46 times than those without any prophylaxis. CONCLUSION: The HCPs found IVR to have a greater risk reduction than with HCQ; while the combination showed the greatest reduction and lack of CP use was associated with a high risk of SARS-CoV-2 infection.


Assuntos
COVID-19 , Médicos , COVID-19/tratamento farmacológico , Humanos , Hidroxicloroquina/uso terapêutico , Ivermectina , Pandemias , Percepção , SARS-CoV-2 , Inquéritos e Questionários
16.
J Am Vet Med Assoc ; 259(8): 914-918, 2021 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-34609187

RESUMO

CASE DESCRIPTION: 2 Nigerian Dwarf goats (a doe [goat 1] and a wether [goat 2]) with coughing and nasal discharge since they were purchased at an auction 6 days prior were empirically treated for suspected pneumonia and intestinal parasitism. An ivermectin dosing error (intended dose, 0.4 mg/kg, PO; administered dose, 10 mg/kg, PO) was retrospectively discovered, and the owner was urged to return the goats for hospitalization and treatment. CLINICAL FINDINGS: On admission 19 hours after iatrogenic ivermectin overdose, both goats had tachycardia, tachypnea, and absent menace responses. Goat 1 also had vomited in transit, was lethargic and febrile, had slow pupillary light reflexes, and walked into walls and obstacles. Goat 2 was quiet but responsive, not ataxic or febrile, and had pale mucous membranes and a prolonged capillary refill time. TREATMENT AND OUTCOME: Each goat received 20% IV lipid emulsion (2 mL/kg, IV bolus over 15 minutes, followed by 0.008 mL/kg/min, IV) and immediately improved. Activated charcoal was administered by orogastric tube, and 6 hours later, mineral oil was similarly administered. Goat 1 had complete resolution of signs and was discharged by 48 and 72 hours, respectively, after admission. Goat 2 improved but developed progressive respiratory distress after the second orogastric intubation and was euthanized. Necropsy findings were consistent with acute renal tubular necrosis, acute respiratory distress syndrome of unknown cause, ruminal tympany, and mesenteric caseous lymphadenitis. CLINICAL RELEVANCE: Results indicated that IV lipid emulsion could be used to successfully treat ivermectin toxicosis in goats. Treatment early in the course of ivermectin toxicosis is advisable to avoid severe clinical signs and secondary complications.


Assuntos
Doenças das Cabras , Ivermectina , Animais , Emulsões Gordurosas Intravenosas/uso terapêutico , Doenças das Cabras/induzido quimicamente , Doenças das Cabras/tratamento farmacológico , Cabras , Ivermectina/toxicidade , Masculino , Estudos Retrospectivos , Taquicardia/veterinária
17.
Toxicon ; 203: 115-116, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34662630

RESUMO

The aim of the present study was to describe an outbreak of poisoning by abamectin in calves less than four months of age whose mothers were treated with a pour-on product containing this ingredient. The diagnosis was based on the history, clinical signs, absence of macroscopic and histopathological findings (characteristic of this type of poisoning) and the detection of abamectin in tissues of the animals submitted to necropsy. Based on this report, the recommendation is the use with caution of pour-on formulations containing abamectin on cows having given birth less than four months earlier.


Assuntos
Anti-Helmínticos , Doenças dos Bovinos , Animais , Bovinos , Doenças dos Bovinos/induzido quimicamente , Doenças dos Bovinos/tratamento farmacológico , Feminino , Ivermectina/análogos & derivados , Ivermectina/toxicidade
18.
Langmuir ; 37(41): 12179-12187, 2021 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-34632776

RESUMO

Avermectin (AVM) is a highly effective and safe biopesticide but is very sensitive to ultraviolet (UV) light and exhibits poor water solubility. Developing green and multifunctional adjuvants is important for the protection and controlled release of AVM. In this work, a number of water-soluble enzymatic hydrolysis lignins (W-EHLs) were prepared via grafting basic amino acids and used as emulsifiers with co-surfactants to prepare high-internal phase emulsions (HIPEs). The results showed that W-EHLs with co-surfactants could be prepared with HIPEs that contained 90 vol % green oil phases such as turpentine, and the stability of the HIPEs first increased and then decreased when the rate of grafting of basic amino acids on lignin increased from 0.26 to 1.46 mmol/g. The more polar oil droplets were less deformable due to their higher viscosity, thereby affording a stability advantage to HIPEs. Subsequently, the relations between the stability and interfacial viscoelasticity of the emulsion were effectively correlated by interfacial rheology, droplet size, and physical stability tests. The results showed that HIPEs with smaller droplets had poor fluidity and strong interfacial viscoelasticity due to their higher droplet packing density, which resulted in good macroscopic stability. Like the AVM carrier, the retention rate of AVM in HIPEs was 80.1% after UV radiation for 72 h, which represented the highest UV protection efficiency in AVM delivery systems. The release curves showed that the rate of release of AVM from HIPEs was adjusted by controlling the pH value of the medium. In addition, the release of HIPEs is completely in accord with both diffusion and the matrix erosion mechanism. The strategy could be extended to other sensitive pesticides and used to promote the development of sustainable agriculture.


Assuntos
Aminoácidos Básicos , Lignina , Biomassa , Preparações de Ação Retardada , Emulsões , Ivermectina/análogos & derivados
19.
Phys Chem Chem Phys ; 23(40): 22957-22971, 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34636373

RESUMO

The identification of chemical compounds able to bind specific sites of the human/viral proteins involved in the SARS-CoV-2 infection cycle is a prerequisite to design effective antiviral drugs. Here we conduct a molecular dynamics study with the aim to assess the interactions of ivermectin, an antiparasitic drug with broad-spectrum antiviral activity, with the human Angiotensin-Converting Enzyme 2 (ACE2), the viral 3CLpro and PLpro proteases, and the viral SARS Unique Domain (SUD). The drug/target interactions have been characterized in silico by describing the nature of the non-covalent interactions found and by measuring the extent of their time duration along the MD simulation. Results reveal that the ACE2 protein and the ACE2/RBD aggregates form the most persistent interactions with ivermectin, while the binding with the remaining viral proteins is more limited and unspecific.


Assuntos
Enzima de Conversão de Angiotensina 2/metabolismo , Antivirais/metabolismo , Proteases 3C de Coronavírus/metabolismo , Proteases Semelhantes à Papaína de Coronavírus/metabolismo , Ivermectina/metabolismo , Enzima de Conversão de Angiotensina 2/química , Antivirais/química , Sítios de Ligação , Proteases 3C de Coronavírus/química , Proteases Semelhantes à Papaína de Coronavírus/química , Quadruplex G , Humanos , Ligação de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Ivermectina/química , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Ligação Proteica , Domínios Proteicos , RNA/genética , RNA/metabolismo , SARS-CoV-2
20.
PLoS One ; 16(10): e0258185, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34644335

RESUMO

Ivermectin is a broad-spectrum antiparasitic medicine, which is often used as a treatment for parasites or as a prophylaxis. While studies have looked at the long-term effects of Ivermectin on helminths, studies have not considered the long-term impacts of this treatment on host health or disease susceptibility. Here, we tracked the effects of early life Ivermectin treatment in Cuban tree frogs (Osteopilus septentrionalis) on growth rates, mortality, metabolically expensive organ size, and susceptibility to Batrachochytrium dendrobatidis (Bd) infection. One year after exposure, there was no effect of Ivermectin exposure on frog mass (X21 = 0.904, p = 0.34), but when tracked through the exponential growth phase (~2.5 years) the Ivermectin exposed individuals had lower growth rates and were ultimately smaller (X21 = 7.78, p = 0.005; X21 = 5.36, p = 0.02, respectively). These results indicate that early life exposure is likely to have unintended impacts on organismal growth and potentially reproductive fitness. Additionally, we exposed frogs to Bd, a pathogenic fungus that has decimated amphibian populations globally, and found early life exposure to Ivermectin decreased disease susceptibility (disease load: X21 = 17.57, p = 0.0002) and prevalence (control: 55%; Ivermectin: 22%) over 2 years after exposure. More research is needed to understand the underlying mechanism behind this phenomenon. Given that Ivermectin exposure altered disease susceptibility, proper controls should be implemented when utilizing this drug as an antiparasitic treatment in research studies.


Assuntos
Anuros/crescimento & desenvolvimento , Anuros/microbiologia , Ivermectina/uso terapêutico , Micoses/tratamento farmacológico , Micoses/veterinária , Animais , Batrachochytrium/efeitos dos fármacos , Suscetibilidade a Doenças , Metamorfose Biológica/efeitos dos fármacos
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