Terpenoids and phenolic compounds from Asteraceae: Potential role in the development of new treatments for arthropod-borne viral diseases caused by flavivirus

Abstract

Vector-borne diseases are human diseases caused by viruses, parasites, or bacteria that are transmitted by vectors.According to statistical data from the World Health Organization (WHO), vector-borne diseases account for more than17% of all infectious diseases and cause more than 700000 deaths each year. These diseases occur mainly in tropicaland subtropical areas, and generally affect the poorest populations (1).Vector-borne diseases caused by arboviruses represent a serious problem worldwide. An estimated 4 million peoplecurrently live in areas where arboviral diseases represent a major cause of public health risk (2). Flaviviridae is a familyof arthropod-borne enveloped RNA viruses that contain important human pathogens such as dengue fever (DENV),yellow fever (YFV), Zika (ZIKV), Japanese encephalitis (JEV), tick-borne encephalitis (TBEV), and West Nile (WNV) virus.According to the WHO, all human diseases caused by arboviruses of the genus Orthoflavivirus are arthropod-bornediseases transmitted mainly by Aedes mosquitoes, being A. aegypti the most common vector (1). Among them, DENVand ZIKV are also classified by the Pan American Health Organization (PAHO) as neglected vector-borne diseases (3).Although these arboviruses mainly affect poor populations in rural areas, they also affect large urban centers (3), andhave been responsible for the main outbreaks of vector-borne viral diseases in recent decades. In addition, theseillnesses are difficult to eradicate because the infectious agents are maintained in nature through spread betweenvectors and hosts, without human-human contact (4). Although there are vaccines for some of these arboviral diseases,there are no specific antiviral agents for their treatment (5-7). Vaccines and synthetic antiviral drugs are frequentlyexpensive, making them inaccessible to most of the world´s population. In this sense, natural compounds may be a goodalternative for developing novel drugs.Natural products have been the main sources of many of the drugs currently used in therapeutics. There is evidencedocumenting the activity of natural compounds against different viruses (8,9). In addition to this, the role of naturalproducts as immunomodulatory agents has been highlighted, increasing protection and resistance against viralinfectious (10,11). In this sense, terpenoids and phenolic compounds, found in Asteraceae, become relevant (9, 12-14).The Asteraceae family is comprised by 1600-1700 genera and around 24000 species, being the family with the largestnumber of species among vascular plants worldwide (15). Moreover, the Asteraceae have a wide variety ofethnomedical and medicinal uses.This chapter aims to present a review of the natural phenolic compounds and terpenoids isolated from Asteraceaeplants, in the last ten years, which can be used as potential drugs for the development of new treatments for humanarboviral diseases transmitted by arthropod vectors caused by flavivirus: DENV, YFV, ZIKV, JEV, TBEV, and WNV. Inaddition, this chapter intends to analyze the activity exerted by these bioactive compounds in the different stages ofthe multiplication cycle of infectious agents, including viral entry, replication, assembly and/or release, as well as specificvirus-host interactions. A discussion of the activity of terpenoid and flavonoid types and the relationship to structuresand substitution patterns will also be included.