Hydroxychloroquine Inhibits Zika Virus NS2B-NS3 Protease

• Published in: ACS omega Vol. 3; no. 12; pp. 18132 - 18141
• Main Authors: Kumar, Ankur, Liang, Brooke, Aarthy, Murali, Singh, Sanjeev Kumar, Garg, Neha, Mysorekar, Indira U, Giri, Rajanish
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 31.12.2018
• ISSN: 2470-1343; 2470-1343
• DOI: 10.1021/acsomega.8b01002

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 (K i) of 92.34 ± 11.91 μM. Additionally, hydroxychloroquine significantly decreases Zika virus infection in placental cells.