Progress for Antiviral Development in Latin America

CASTILLA V; DAMONTE EB; GARCÍA CC; SEPÚLVEDA CS

Human Virology in Latin America

Springer

Año: 2017; p. 439 - 460

The search of novel effective antiviral agents for treatment of viral infections is a constant challenge for human health. Even when successful drugs have been developed and employed to combat well-known human pathogens, many current therapies face the difficulty of a high rate of genetic change exhibited by viruses, enabling the selection of drug-resistant mutants. This shift adds to the increasing periodic emergence of new viral pathogens or the reemergence of old ones lacking a reliable drug therapy. Therefore, the finding of new antiviral approaches is a continuously demanding effort.In Latin America, antiviral research has been mainly focused on herpes simplex virus (HSV) as a global model system of antiviral studies because resistance to acyclovir, the currently standard antiherpetic agent, is still a therapeutic challenge, particularly for immunocompromised patients requiring prolonged treatment [110].Viruses causing neglected diseases represent a serious threat for public health in the region, such as dengue virus (DENV) [72]. Junín virus (JUNV), the agent of A partially purified extract (MA) from the leaves of Melia azedarach L. Exhibited a potent antiviral effect against several RNA and DNA viruses. MA impaired DNA synthesis and virus assembly in HSV-1-infected cultures, whereas in vivo studies demonstrated that this active principle prevented the development of herpetic stromal keratitis (HSK) in mice and exhibited protective effect in a mouse model of genital HSV-2 infection [7, 104]. The tetranortriterpenoid 1-Cinnamoyl-3,11-dihydroxymeliacarpin (CDM) was then identified as the molecule responsible for the broad spectrum of MA action. CDM blocked intracellular transport of viral HSV-1 glycoproteins and altered cytokine production in infected conjunctival and corneal cells by blocking NF-κB pathway activation [14, 23] and in HSV-stimulated macrophages by an NF-κB independent pathway [105].Remarkably, diterpenes isolated from Euphorbia laurifolia and E. lacteal were able to induce human immunodeficiency virus (HIV) reactivation in an in vitro latency system, suggesting that these molecules would be useful, in combination with highly active antiretroviral therapy, to eradicate the pool of latently HIV-infected CD4+ T cells [13].On the other hand, nordihydroguaiaretic acid (NDGA), the main metabolite ofthe creosote bush (Larrea tridentata), inhibited DENV infection by reduction ofviral genome replication and inhibition of virion assembly by its ability to reduce the levels of cell lipid droplets, structures where virus assembly takes place [132].Table 1 summarizes the antiviral spectrum of main plant-derived compounds studied by Latin American researchers and includes information about other molecules of plant origin such as polysaccharides that were chemically sulfated [49, 98], alkaloids [39, 76], cardenolides [16], and the antioxidant compound gallic acid [67].