Atividade antiviral de compostos naturais brasileiros e hidroxichalconas e curcuminoides sintéticos

Abstract

The human papilloma virus (HPV) is responsible for a sexually transmitted disease of high prevalence worldwide. HPV is directly related to several types of cancer, such as cervical cancer. Although there is approaches to the treatment of HPV-associated lesions and prophylactic vaccines to prevent virus infection, there are no reports of treatment against the infection. Synthetic compounds derived from natural substances are an interesting source for the development of new antiviral treatments. In this context, molecules derived from the classes of the hydroxychalcones and curcuminoids have attracted interest due to the diverse effects against bacterial, fungal and viral infections. These effects added to the large-scale production capacity of the synthetic components, have a promising cost-benefit relation for the development of new antivirals. Thus, the present work aimed to evaluate the activity of synthetic hydroxychalcones and curcuminoids in HPV infection in vitro. To evaluate the effect of these compounds on virus infection, HPV pseudoviruses were produced using 293T cells transfected with plasmids p16SHELL and pClneoEGFP, which express the capsid L1 and L2 proteins and green fluorescent protein (EGFP), respectively. Subsequently, 293T cells were infected with the pseudoviruses produced in the presence or absence of the compounds, in non-toxic concentrations, to evaluate the effect of the treatment on infection. The results demonstrated that pseudoviruses were able to infect 293T cells and express fluorescence, however, the compounds evaluated in this work did not show statistically significant effects on inhibition of HPV infection.The Chikungunya virus (CHIKV) was discovered in Tanzania in 1950 and is responsible for Chikungunya fever, causing severe muscle and joint pain, fever and nausea. According to the Pan American Health Organization (PAHO), in the year 2017, about 120,000 cases of Chikungunya fever in the Americas were confirmed. The major problem with infection is the possibility of chronification. The disease is endemic and has no specific or prophylactic treatments, such as vaccines. The treatment is made from palliative measures with analgesics and antipyretics. In this context, natural compounds may provide an alternative source for the identification of products with therapeutic potential. Compounds originating from animal poisons have demonstrated antiviral activity against other viruses, such as dengue virus (DENV), yellow fever (YFV) and measles. In addition, some current treatments such as hypertension were based on isolated compounds of snake venom. Therefore, the present work had as objective to evaluate the activity of proteins isolated from venom of snakes of the genus Crotalus sp and Bothrops sp in the replicative cycle of CHIKV in vitro. Cell viability and infectivity assays were performed on BHK-21 cells, and replication assays on BH-21 cells expressing the CHIKV-NCT subgenomic replicon. The results demonstrated that the PLA protein showed statistically significant antiviral activity, inhibiting 81% of the CHIKV infectivity. This study demonstrated for the first time the activity of the PLA protein in the replicative cycle of CHIKV, and proposes a new substance as a promising form of fighting the virus.