Memantine hydrochloride: a drug to be repurposed against Chikungunya virus?

BACKGROUND: Chikungunya fever is an endemic disease caused by the Chikungunya virus (CHIKV) to which there is no vaccine or effective antiviral drug treatment so far. Our study aimed to evaluate the potential anti-CHIKV activity of memantine hydrochloride (mtnH), a drug from the class of the aminoadamantanes approved for the treatment of Alzheimer´s disease, as a possible drug to be repurposed to the treatment of Chikungunya fever. METHODS: MtnH antiviral activity against CHIKV was determined by infecting BHK-21 cells with CHIKV-nanoluc, a virus carrying the marker nanoluciferase reporter, in the presence or absence of mtnH at concentrations ranging from 500 to 1.45 µM. The effective concentration of 50% inhibition (EC50) was calculated. Cell viability assay (determination of CC50) was also performed employing BHK-21 cells. Mutagenic assays were performed by the Salmonella Typhimurium/microsome assay (Ames test). RESULTS: MtnH presented a CC50 of 248.4 ± 31.9 µM and an EC50 of 32.4 ± 4 µM against CHIKV in vitro. The calculated selectivity index (SI) was 7.67. MtnH did not induce genetic mutation in Salmonella strains with or without an external metabolizing system. CONCLUSION: With the data herein presented, it is possible to hypothesize mtnH as a viable candidate to be repurposed as an anti-CHIKV drug. Clinical assays are, therefore, encouraged due to the promising in vitro results. The drug memantine hydrochloride is herein personified with a doubt: as a prior regulated drug against Alzheimer, could it follow the path against Chikungunya virus too?

Efficacy of extracts of immature mango on ovine gastrointestinal nematodes.

The principal health problem in small ruminants is helminthiasis and the rapid development of nematode resistance to anthelminthics has limited the success of control in several countries, stimulating the search for alternatives. In this study, extracts of immature fruits of the mango Mangifera indica L. var Ubá were evaluated for inhibition of larval development and fecal egg count reduction in sheep naturally infected with gastrointestinal nematodes. In the phytochemical analyses, tannins and flavonoids were the metabolites identified. Aqueous extracts of immature fruits at 100 mg ml(-1) showed 100 % inhibition of larval development. The LC(90) of the extract was 35.9 mg ml(-1) and the in vivo anthelminthic efficacy at 0.740 g kg(-1) (BW, orally) was 53 %. The identification of larvae showed that 99.8 % were Haemonchus spp. In vitro and in vivo results indicate that this fruit could assist ovine nematode control.

Ocorrência e tratamento de miíases cutâneas em ovinos criados em condições semiáridas no norte de Minas Gerais / Occurrence and treatment of cutaneous myiasis in sheep reared in semi-arid conditions in northern Minas Gerais

A ocorrência de miíases cutâneas foi verificada em 10 diferentes criatórios de ovinos no norte de Minas Gerais, Brasil, durante o período de um ano, onde foram analisados os fatores relacionados a essas parasitoses. Os rebanhos possuíam predominantemente animais mestiços Santa Inês, criados em sistemas semiextensivo. Foram registrados 50 casos e a maior incidência foi observada nos meses de março (22%) e abril (18%), períodos de maiores temperaturas e umidade relativa do ar. As patas foram as regiões mais frequentemente acometidas (34% dos casos). As lesões por pododermatites (38% dos casos), onfaloflebites (10%), linfadenite (6%) e dermatobiose (6%) foram os fatores mais frequentemente relacionados às miíases. As taxas de ocorrência não diferiram quanto ao sexo e idade dos animais. Foi constatado que a maioria dos proprietários não realizava o tratamento das miíases de forma correta, sendo que após a implantação de uma terapia preconizada nesta pesquisa, 92% das lesões apresentaram cura entre sete e trinta dias. Os resultados apontam a importância de estratégias para prevenção baseadas nos fatores relacionados neste estudo. A inspeção constante dos ovinos, identificando-se os ferimentos e tratando-se as lesões precocemente, devem constituir práticas rotineiras, principalmente no período chuvoso e quando estão presentes nas patas dos animais.

Cutaneous myiasis was investigated in 10 sheep herds during one year in northern Minas Gerais, Brazil, and factors related to its occurrence were analyzed. The sheep were predominantly hybrid Saint Inês, bred in semi-extensive systems. A total of 50 cases were registered and the highest incidence occurred during March (22%) and April (18%), months with high temperatures and high relative humidity of the air. There was no influence of sex and age for the occurrence of myiasis. The lesions were mostly found on the legs (34% of the cases). Pododermatitis (38% of the cases), omphalophlebitis (10%), lymphadenitis (6%) and dermatobiosis (6%) were the predisposing factors more frequently associated with myiasis. The myiasis was not correctly treated by the owners, but after implantation of a correct therapy, 92% of the lesions presented cure within 7 to 30 days. The results show the importance of preventive strategies based on the predisposing factors identified in this study. The constant inspection, identifying wounds and precociously treating the lesions, should be routine especially at the end of rainy season and when predisposing factors are present.

In vitro and in vivo efficacy of aqueous extract of Caryocar brasiliense Camb. to control gastrointestinal nematodes in sheep.

A major problem faced in sheep rearing has been the rapid acquisition of anthelminthic-resistant populations of gastrointestinal nematodes. In the search for alternatives, aqueous extract of the peel of Caryocar brasiliense was evaluated for larval development inhibition, egg-hatching inhibition, and fecal nematode egg count reduction in sheep. For in vivo analysis, the doses were calculated according to a 10% lethal dose derived from acute toxicity tests in mice, and the efficacy was evaluated for two periods following oral administration of the extract. Egg-hatching inhibition at concentrations of 15 and 7.5 mg/ml was significantly higher than observed in negative controls with distilled water. For larval development inhibition, all concentrations showed anthelminthic activity significantly higher than controls and were not significantly different from ivermectin treatment. The LC(90) of larval development inhibition was 53.19 mg/ml. In vivo analysis for first and second weeks after treatment found 32.2% and 33% anthelminthic efficacy, respectively.

Diagnóstico do controle e perfil de sensibilidade de nematódeos de ovinos ao albendazol e ao levamisol no norte de Minas Gerais / Diagnostic of the control and sensitivity profile of nematodes from sheep to albendazole and levamisole in northern Minas Gerais, Brazil

A resistência anti-helmíntica é um dos principais entraves para o controle da verminose em ruminantes e a presença de nematódeos multiresistentes pode inviabilizar a atividade em uma determinada área. Neste trabalho o objetivo foi avaliar a eficácia anti-helmíntica do levamisol e do albendazol em rebanhos ovinos do norte de Minas Gerais. O teste foi realizado em dez propriedades, onde foram selecionados três grupos de 12 borregos cada. Dois desses grupos foram tratados respectivamente com levamisol (5 mg/kg pc) ou albendazol (10 mg/kg pc) e o terceiro grupo não foi tratado. Fezes foram coletadas antes do tratamento e no sétimo dia após, para a realização do teste de redução de ovos por grama de fezes. Foi realizado o cultivo de larvas provenientes dos grupos avaliados para a identificação dos principais gêneros de nematódeos gastrintestinais antes e após os tratamentos. Para todos os rebanhos avaliados no norte de Minas Gerais, o levamisol apresentou eficácia anti-helmíntica elevada, variando de 90% a 100%. Apenas para um rebanho o albendazol seria efetivo e para seis propriedades as eficácias dessa droga foram inferiores a 80%, sendo considerada insuficientemente ativa. Após as coproculturas foram identificadas, em maior ocorrência, larvas dos gêneros Haemonchus e Trichostrongylus. O gênero Haemonchus foi o mais prevalente mesmo após o tratamento dos ovinos. Ressalta-se neste estudo a importância do teste de eficácia in vivo para a escolha das bases anti-helmínticas nas propriedades, pois foi observado que o perfil de susceptibilidade variou entre os diferentes rebanhos.

The anthelmintic resistance is a major obstacle for the nematode control in ruminants and the presence of multiresistant nematodes could make impracticable the activity in a given area. The objective in this study was to evaluate the anthelmintic efficacy of albendazole and levamisole in sheep herds in northern Minas Gerais. The test was performed on ten farms, where we selected three groups of 12 lambs each. Two of these groups were respectively treated with levamisole (5mg/kg) or albendazole (10mg/kg). The third group did not receive treatment. Feces were collected at 0 and 7 day after treatment for the fecal egg reduction test. The nematode genus was evaluated with the identification of the larvae obtained from culture in the feces pre- and post-treatments. For all evaluated herds the levamisole showed high anthelminthic efficacy, which ranged from 90 to 100%. Only for one herd, the albendazole was effective and for six farms, the efficacy of this drug was less than 80%, considered insufficiently active. After the cultivation of larvae were identified mainly Haemonchus spp. and Trichostrongylus spp. The genus Haemonchus was the most prevalent even after treatment of sheep. It is emphasized the importance of in vivo efficacy tests for choosing anthelmintic drugs, since the susceptibility profile varied among sheep herds evaluated in this study.