IIT Mandi Researchers Discover New Drug Against Zika Virus
Till date, Millions of people have been affected by the Zika Virus. A group of researchers at IIT- Mandi lead by Dr. Rajanish Giri, Assistant Professor of Biotechnology have discovered a drug target in Zika virus that has the capability to attach to an existing antimalarial drug to halt the spread of the infection throughout the human body.
Earlier scientists at Washington University, the USA under the direction of Prof Indira Mysorekar had discovered that an antimalarial drug – hydroxychloroquine (HCQ) reduces the chance of the ZIKV transmission from mother to fetus. Working ahead on this lead, scientists at Prof Giri’s lab have located the target viral protein upon which the HCQ drug acts.
Zika virus is included in the WHO’s top 10 global threat against health 2019 list, showcasing the severity of this virus. It belongs to the genus Flavivirus along with dengue virus, yellow fever virus, and Japanese Encephalitis virus. The symptoms of ZIKV infections are severe headaches, lethargy often associated with various neurological disorders as well. Upon passed on to the fetus by the mother the child can suffer from a deadly disease called microcephaly.
In order to block the ZIKV activity a crucial an enzyme called – NS2B-NS3 protease was targeted under the study. The enzyme plays the role of governing polyprotein maturation – viral multiplication, leading to survival and pathogenesis of the virus.
High throughput virtual screening of FDA approved drug library was done in order to identify molecules that can inhibit the actions of NS2B-NS3 protease. Five compounds that showed up had a prominent affinity towards the protease out of which one compound was HCQ. The HCQ compound was further validated by molecular dynamics simulations.
Zika virus gene construct was cloned by the scientists and its NS2B-NS3 protease enzyme was purified & expressed. The study shows that HCQ bonded with the NS2B-NS3 protease complex, thus competitively inhibiting its ability to contribute to viral multiplication.
Prof Sanjeev Kumar Singh from Alagappa University, Tamil Nadu also joined the IIT Mandi team in this research study, the findings of which were published in the American Chemical Society journal.