ABSTRACT
Mayaro fever, caused by Mayaro virus (MAYV) is a sub-lethal disease with symptoms that are easily confused with those of dengue fever, except for polyarthralgia, which may culminate in physical incapacitation. Recently, outbreaks of MAYV have been documented in metropolitan areas, and to date, there is no therapy or vaccine available. Moreover, there is no information regarding the three-dimensional structure of the viral proteins of MAYV, which is important in the search for antivirals. In this work, we constructed a three-dimensional model of protein C of MAYV by homology modelling, and this was employed in a manner similar to that of receptors in virtual screening studies to evaluate 590 molecules as prospective antiviral agents. In vitro bioassays were utilized to confirm the potential antiviral activity of the flavonoid epicatechin isolated from Salacia crassifolia (Celastraceae). The virtual screening showed that six flavonoids were promising ligands for protein C. The bioassays showed potent antiviral action of epicatechin, which protected the cells from almost all of the effects of viral infection. An effective concentration (EC50) of 0.247 µmol/mL was observed with a selectivity index (SI) of 7. The cytotoxicity assay showed that epicatechin has low toxicity, with a 50% cytotoxic concentration (CC50) greater than 1.723 µmol/mL. Epicatechin was found to be twice as potent as the reference antiviral ribavirin. Furthermore, a replication kinetics assay showed a strong inhibitory effect of epicatechin on MAYV growth, with a reduction of at least four logs in virus production. Our results indicate that epicatechin is a promising candidate for further testing as an antiviral agent against Mayaro virus and other alphaviruses.
Subject(s)
Alphavirus/chemistry , Antigens, Viral/chemistry , Antiviral Agents/pharmacology , Catechin/pharmacology , Salacia/chemistry , Viral Proteins/chemistry , Alphavirus/metabolism , Animals , Antigens, Viral/metabolism , Antiviral Agents/chemistry , Antiviral Agents/isolation & purification , Binding Sites , Catechin/chemistry , Catechin/isolation & purification , Chlorocebus aethiops , High-Throughput Screening Assays , Humans , Inhibitory Concentration 50 , Molecular Docking Simulation , Protein Binding , Protein Conformation, alpha-Helical , Protein Conformation, beta-Strand , Protein Interaction Domains and Motifs , Ribavirin/chemistry , Ribavirin/pharmacology , Structural Homology, Protein , User-Computer Interface , Vero Cells , Viral Proteins/antagonists & inhibitors , Viral Proteins/metabolism , Virus Replication/drug effectsABSTRACT
Maytenus truncata Reiss (Celastraceae) é uma planta nativa da Bahia (Brasil), sendo conhecida como "espinheira-santa". É usada popularmente na forma de decoto das folhas (chás) como antiulcerogênico, similarmente à Maytenus ilicifolia, a verdadeira "espinheira-santa". O objetivo do presente estudo foi avaliar a atividade antiúlcera e cicatrizante, assim como o perfil fitoquímico dos extratos brutos em acetato de etila e metanol da Maytenus truncata. A administração per os desses extratos nas doses de 120 mg/kg e 240 mg/kg reduziu a severidade da lesão gástrica induzida pelo estresse ao frio (-18 °C por 45 minutos) em ratos, com resultados mais significativos para o extrato bruto obtido em metanol. A administração dos extratos provocou o aumento do pH. Os resultados obtidos na administração do extrato bruto em metanol não contrariam seu uso popular, não somente pela atividade observada, mas também por se tratar de um extrato de alta polaridade cujos princípios podem ser obtidos a partir de uma infusão, embora estudos clínicos devam ser realizados para confirmação dessa hipótese.
Maytenus truncata Reiss (Celastraceae) is a native plant from Bahia (Brazil), known as "espinheira-santa". It is popularly used in the form of decoct of leaves (tea) as antiulcerogenic, similarly to Maytenus ilicifolia, the true "espinheira-santa". This study aims to evaluate antiulcerogenic and healing activities, as well as the phytochemical profile, of ethyl acetate and methanol crude extracts of Maytenus truncata. Per os administration of these extracts at 120 mg/kg and 240 mg/kg doses decreased the severity of gastric lesions induced by cold-restraint stress (-18 °C for 45 minutes) in rats, with more significant results for the crude methanol extract. The administration of the extracts caused pH increase. The results obtained with the administration of crude methanol extract are not contrary to its popular use, not only for the activity observed but, also, for its high polarity that enables the obtention of the active principles through infusion, though clinical studies should be performed to confirm this assertion.
ABSTRACT
Four new N-alkyl-2-mercapto-1-octylamine hydrochlorides were synthesized via the reaction of 1,2-epithio-octane with corresponding amines following by conversion to the hydrochlorides. The disulfides were obtained by oxidation of the respective thiols. Upon biological assay of the products for activity against infection by Schistosoma mansoni, only 2,2'-dithiobis(N-isobutyl-1-octylamine) exhibited activity.
