Hydroxychloroquine Inhibits Zika Virus NS2B-NS3 Protease

Zika virus is a mosquito-transmitted flavivirus that causes devastating fetal outcomes in the context of maternal infection during pregnancy. An important target for drugs combatting Zika virus pathogenicity is NS2B-NS3 protease, which plays an essential role in hydrolysis and maturation of the flavivirus polyprotein. We identify hydroxychloroquine, a drug that already has approved uses in pregnancy, as a possible inhibitor of NS2B-NS3 protease by using a Food and Drug Administration-approved drug library, molecular docking, and molecular dynamics simulations. Further, to gain insight into its inhibitory potential toward NS2B-NS3 protease, we performed enzyme kinetic studies, which revealed that hydroxychloroquine inhibits protease activity with an inhibition constant (Ki) of 92.34 ± 11.91 μM. Additionally, hydroxychloroquine significantly decreases Zika virus infection in placental cells.

Abstract licence: CC BY-NC-ND

1. 8.

   DrugBank 4.0: shedding new light on drug metabolism · 2013

2. 10.

   Structure and functionality in flavivirus NS-proteins: Perspectives for drug design · 2010

3. 24.

   Genetic and Serologic Properties of Zika Virus Associated with an Epidemic, Yap State, Micronesia, 2007 · 2008

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