The Medicinal Chemistry of Zika Virus

Arthropod-borne viruses, also known as arboviruses, are transmitted by bites of infected mosquito or tick vectors. In this context, the Flavivirus genus is mainly transmitted by mosquitoes from the Aedes genus, being the Ae. africanus, Ae. aegypti, and Ae. Albopictus species are responsible for transmitting the Zika virus (ZIKV). It is a lipid-enveloped virus constitute of an RNA genome, which is translated into a polyprotein encoding three structural proteins {(capsid (C), membrane (M), and envelope (E)} and seven non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5). Several biological targets have been identified for developing antiviral agents against ZIKV, which could prevent virus entry, assembly, or release of new virion particles, by interactions with structural proteins. Drugs targeting non-structural proteins could inhibit the ZIKV-replication cycle. Nature has provided excellent compounds for designing new potent analogs. The medicinal chemistry emerges as an impressive, rationally design and to develop new antiviral agents. Additionally, virtual and high-throughput screenings have contributed greatly to the identification of previously approved-drugs that could be repurposed for ZIKV, as antiviral agents. In this chapter, we offer a literature review about the most relevant and recent advances made on the medicinal chemistry of ZIKV research. We focus on natural, nature-based, semi-synthetic, and synthetic antiviral compounds, as well as repurposed drugs and other inhibitors targeting ZIKV.