Kumar Ankur, Liang Brooke, Aarthy Murali, Singh Sanjeev Kumar, Garg Neha, Mysorekar Indira U, Giri Rajanish
Indian Institute of Technology Mandi, Mandi 175005, Himachal Pradesh, India.
Department of Obstetrics and Gynecology, Center for Reproductive Health Sciences, and Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, Missouri 63110, United States.
ACS Omega. 2018 Dec 31;3(12):18132-18141. doi: 10.1021/acsomega.8b01002. Epub 2018 Dec 24.
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 ( ) of 92.34 ± 11.91 μM. Additionally, hydroxychloroquine significantly decreases Zika virus infection in placental cells.
寨卡病毒是一种通过蚊子传播的黄病毒，在孕期母体感染的情况下会导致严重的胎儿不良后果。对抗寨卡病毒致病性的药物的一个重要靶点是NS2B-NS3蛋白酶，它在黄病毒多蛋白的水解和成熟过程中起着至关重要的作用。我们通过使用美国食品药品监督管理局批准的药物库、分子对接和分子动力学模拟，确定了一种已被批准可用于孕期的药物羟氯喹，它可能是NS2B-NS3蛋白酶的抑制剂。此外，为了深入了解其对NS2B-NS3蛋白酶的抑制潜力，我们进行了酶动力学研究，结果表明羟氯喹抑制蛋白酶活性的抑制常数（ ）为92.34 ± 11.91 μM。此外，羟氯喹可显著降低胎盘细胞中的寨卡病毒感染。
