Mechanism and Molecular Interactions of Bioactive molecules with NS3 protease from Zika virus.

Abstract

Since 1981, the Brazilian population has had dengue fever epidemics and all control efforts have been unsuccessful. In 2014, chikungunya fever was reported for the first time in the country. Zika virus was also reported in 2015, along with an increase of microcephaly and brain damage in newborn babies. Literature shows that Flaviviruses cause a variety of diseases, including fevers, encephalitis, and hemorrhagic fevers. NS3 is one of the Non-structural protein presents a multifunctional behaviour with an N-terminal protease domain (NS3pro) that is responsible for proteolytic processing of the viral polyprotein. Therefore, NS3 protein is the preferential choice for inhibition to stop the proteolytic processing. The multiple roles played by the NS2B-NS3 protein in the virus life cycle makes it an attractive target for antiviral drug discovery. The N-terminal region of NS3 and its cofactor NS2B constitute the protease that cleaves the viral polyprotein. No effective antiviral therapy is currently available for treatment of flavivirus infections. Development of antiviral treatment against these viruses is urgently needed. Animals venoms contain a huge variety of molecules affecting vital physiological systems, and these toxins can be a life-saving therapeutics. Since the approval of captopril - the first drug based on snake venom protein - more than 30 years ago, animals venom toxins have become a valuable natural pharmacopeia of bioactive molecules that provide lead compounds for the development of new drugs. A number of new drugs are constantly emerging from this pipeline.