Atividade antiviral de extratos de Maytenus imbricata contra Flavivírus

Abstract

Different families of viruses belong to the arboviruses group known to be transmitted by arthropods. Members of the Flavivirus genus which belongs to the Flaviviridae family, as Dengue virus (DENV) and the Yellow fever virus (YFV), and emerging viruses as St. Louis encephalitis virus (SLEV), are arboviruses with high burden in global public health. Despite the efforts, there is no dengue vaccine, unlike yellow fever, whose vaccine is safe and effective. Antiviral drugs approved against any flaviviruses are unavailable. The treatment consists in supportive care with patient hydration and use of antipyretics. Consequently, there is a clear necessity for safe and effective drugs against these viruses. In this context, plants, and their therapeutic use in popular medicine, have provided the development of several drugs today widely used in the clinic. The Maytenus imbricata species is an endemic plant in Brazil and its antiviral activity was not investigated yet. This study aimed to evaluate the antiviral activity of M. imbricata against DENV-4, SLEV and YFV. Screening of FSEAT, SEM and SEAT extracts obtained from M. imbricata roots against DENV-4, SLEV and YFV was carried out by means of the MTT technique. Selectivity indexes (SI) were obtained ranging from 7,67 to 10,32 for DENV-4; 3.82 to 6.87 for SLEV; and from 5.4 to 8.31 for YFV. In virucidal activity tests against these viruses SI ranging from 13,56 to 20,93 against DENV-4; 9.07 to 19.41 against SLEV; and 11.17 to 13.49 against YFV were obtained. When the extracts were incubated with 106 pfu of virus for 5, 15, 30 minutes and 1 hour, there was a decrease of up to 3 log10 (SEAT against YFV) in viral titer compared to the untreated control, and this action increased to maximum virucidal action after 1h of incubation. The extracts showed no activity in the pre- and post-treatment of in vitro infections. None of the extracts showed significant antiviral activity against other DNA and RNA viruses, enveloped or not. This screening allowed us to also argue that the virucidal activity of the extracts against DENV, SLEV and YFV is not only due the envelope presence since, with the exception of EMC, all other viruses tested presented an envelope. This suggests that active substances of the extracts may have selective action on the Flavivírus viral envelope. The mechanism of action of the antiviral activity of the extracts remains to be elucidated, but it can be concluded that M. imbricata has a potential to continue to be studied. It is advantageous because it presents relevant activity not only against DENV, but also against other flavivíruses without antiviral therapy.