Chloroquine, a FDA-approved Drug, Prevents Zika Virus Infection and its Associated Congenital Microcephaly in Mice
Chunfeng Li,
Xingliang Zhu,
Xue Ji,
Natalie Quanquin,
Yong-Qiang Deng,
Min Tian,
Roghiyh Aliyari,
Xiangyang Zuo,
Ling Yuan,
Shabbir Khan Afridi,
Xiao-Feng Li,
Jae U. Jung,
Karin Nielsen-Saines,
Frank Xiao-Feng Qin,
Cheng-Feng Qin,
Zhiheng Xu,
Genhong Cheng
Affiliations
Chunfeng Li
Center for Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005; Suzhou Institute of Systems Medicine, Suzhou, Jiangsu 215123, China
Xingliang Zhu
State Key Laboratory of Molecular Developmental Biology, CAS Center for Excellence in Brain Science and Intelligence Technology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China
Xue Ji
Guangxi Medical University, Nanning 530021, China
Natalie Quanquin
Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA 90095, USA
Yong-Qiang Deng
Department of Virology, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China
Min Tian
Beijing Traditional Medicine Chinese Hospital, Capital Medical University, Beijing 100069, China
Roghiyh Aliyari
Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA 90095, USA
Xiangyang Zuo
Center for Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005; Suzhou Institute of Systems Medicine, Suzhou, Jiangsu 215123, China
Ling Yuan
State Key Laboratory of Molecular Developmental Biology, CAS Center for Excellence in Brain Science and Intelligence Technology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China
Shabbir Khan Afridi
State Key Laboratory of Molecular Developmental Biology, CAS Center for Excellence in Brain Science and Intelligence Technology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China
Xiao-Feng Li
Department of Virology, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China
Jae U. Jung
Department of Molecular Microbiology and Immunology, University of Southern California, Zilkha Neurogenetic Institute, 1501, 11 San Pablo Street, Los Angeles, CA 90033, USA
Karin Nielsen-Saines
Division of Pediatric Infectious Diseases, David Geffen School of Medicine, University of California, Los Angeles, Marion Davies Children's Health Center, 10833 Le Conte Avenue, Los Angeles, CA 90095, USA
Frank Xiao-Feng Qin
Center for Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005; Suzhou Institute of Systems Medicine, Suzhou, Jiangsu 215123, China
Cheng-Feng Qin
Department of Virology, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China
Zhiheng Xu
State Key Laboratory of Molecular Developmental Biology, CAS Center for Excellence in Brain Science and Intelligence Technology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China
Genhong Cheng
Center for Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005; Suzhou Institute of Systems Medicine, Suzhou, Jiangsu 215123, China
Zika virus (ZIKV) has become a global public health emergency due to its rapidly expanding range and its ability to cause severe congenital defects such as microcephaly. However, there are no FDA-approved therapies or vaccines against ZIKV infection. Through our screening of viral entry inhibitors, we found that chloroquine (CQ), a commonly used antimalarial and a FDA-approved drug that has also been repurposed against other pathogens, could significantly inhibit ZIKV infection in vitro, by blocking virus internalization. We also demonstrated that CQ attenuates ZIKV-associated morbidity and mortality in mice. Finally, we proved that CQ protects fetal mice from microcephaly caused by ZIKV infection. Our methodology of focusing on previously identified antivirals in screens for effectiveness against ZIKV proved to be a rapid and efficient means of discovering new ZIKV therapeutics. Selecting drugs that were previously FDA-approved, such as CQ, also improves the likelihood that they may more quickly reach stages of clinical testing and use by the public.
