THE ZIKA VIRUS IS A MOSQUITO-BORNE EMERGING GLOBAL PATHOGEN BELONGING TO THE FLAVIVIRUS GENUS
DHARAM PRAKASH GUPTA
The researchers of Indian Institute of Technology Mandi have made headway in finding a drug to treat the Zika virus (ZIKV) that has affected more than a million people across the world. A team led by Dr. Rajanish Giri, Assistant Professor of Biotechnology, IIT Mandi, is working on this subject.Following an earlier finding by Prof. Indira Mysorekar from the Washington University at St. Louis, USA, that hydroxychloroquine (HCQ), a drug commonly prescribed for treating malaria, reduces ZIKV transmission from mother to foetus, Prof. Giri’s from the IIT has identified the target viral protein on which HCQ acts. Prof. Giri has collaborated with Prof. Mysorekar and Prof. Sanjeev Kumar Singh from Alagappa University, Tamil Nadu, on this work and their findings have recently been published in ACS Omega, an Open Access journal of the American Chemical Society. The Zika virus is a mosquito-borne emerging global pathogen belonging to the flavivirus genus. Other members of this genus include dengue virus, yellow fever virus, and Japanese Encephalitis virus. ZIKV infection leads to fever, headaches, lethargy, conjunctivitis-like symptoms and may even be associated with neurological diseases such as Guillain-Barré syndrome.
Telling about his findings, Prof. Giri said, “Our work has identified a viral protein on which HCQ acts and this finding is important as development of drugs against ZIKV hinges on understanding the interactions between the potential drug and the target components of the virus”.“To block Zika virus activity we targeted an important enzyme called protease. It is enzyme governs the polyprotein maturation, leading to survival and pathogenesis of the virus,” says Prof. Giri. “Repurposing approved drugs can be an efficient method to identify drug compounds, which may be capable of activating or inhibiting new targets”, the researchers tell. The research team have designed and cloned the protease gene construct of the Zika virus and expressed and purified its NS2B-NS3 protease enzyme. HCQ inhibited the enzyme activity, showing that HCQ is a promising drug for ZIKV infection. Understanding the interactions between molecules such as HCQ and important viral enzymes such as proteases is an important step in the development of drugs that can attack the virus and prevent it from multiplying in the host cells. Drawing inspiration from earlier studies in this area, Prof. Giri and his team have identified potential candidates within existing banks of drugs that stop the growth and spread of the Zika virus within the host. In future, this discovery may hasten implementation of effective therapies against ZIKV infections.
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