An adenosine nucleoside inhibitor of dengue virus.

Proceedings of the National Academy of Sciences of the United States of America
Zheng YinPei-Yong Shi

Abstract

Dengue virus (DENV), a mosquito-borne flavivirus, is a major public health threat. The virus poses risk to 2.5 billion people worldwide and causes 50 to 100 million human infections each year. Neither a vaccine nor an antiviral therapy is currently available for prevention and treatment of DENV infection. Here, we report a previously undescribed adenosine analog, NITD008, that potently inhibits DENV both in vitro and in vivo. In addition to the 4 serotypes of DENV, NITD008 inhibits other flaviviruses, including West Nile virus, yellow fever virus, and Powassan virus. The compound also suppresses hepatitis C virus, but it does not inhibit nonflaviviruses, such as Western equine encephalitis virus and vesicular stomatitis virus. A triphosphate form of NITD008 directly inhibits the RNA-dependent RNA polymerase activity of DENV, indicating that the compound functions as a chain terminator during viral RNA synthesis. NITD008 has good in vivo pharmacokinetic properties and is biologically available through oral administration. Treatment of DENV-infected mice with NITD008 suppressed peak viremia, reduced cytokine elevation, and completely prevented the infected mice from death. No observed adverse effect level (NOAEL) was achieved whe...Continue Reading

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Citations

Mar 8, 2013·Applied Microbiology and Biotechnology·Xiao-Feng LiCheng-Feng Qin
Feb 11, 2011·Current Infectious Disease Reports·Annelies Wilder-SmithDuane J Gubler
Mar 9, 2013·Antiviral Research·Tine De BurghgraeveJohan Neyts
Aug 22, 2012·Proceedings of the National Academy of Sciences of the United States of America·John W SchogginsCharles M Rice
Feb 26, 2011·The Journal of Biological Chemistry·Gang ZouPei-Yong Shi
Oct 27, 2010·Assay and Drug Development Technologies·David ShumHakim Djaballah
Jul 19, 2012·The Journal of Infectious Diseases·Nguyet Minh NguyenCameron P Simmons
Jun 23, 2012·Science Translational Medicine·Ee Ping TeohPaul A MacAry
May 12, 2010·Antimicrobial Agents and Chemotherapy·Yen-Liang ChenPei-Yong Shi
Jun 3, 2010·Antimicrobial Agents and Chemotherapy·Yen-Liang ChenPei-Yong Shi
Jul 8, 2010·Antimicrobial Agents and Chemotherapy·Min QingPei-Yong Shi
Jul 7, 2011·Antimicrobial Agents and Chemotherapy·Qing-Yin WangPei-Yong Shi
Sep 15, 2010·Antimicrobial Agents and Chemotherapy·Suzanne J F KapteinJohan Neyts
Jul 5, 2013·Journal of Virology·Matthew A FischerKlaus Früh
Oct 22, 2010·Journal of Virology·Jason KerkvlietMoses Rodriguez
Mar 20, 2010·Journal of Virology·Pornwaratt NiyomrattanakitPei-Yong Shi
Apr 22, 2011·Journal of Virology·Qing-Yin WangPei-Yong Shi
Aug 26, 2011·Journal of Virology·Xuping XiePei-Yong Shi
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Sep 26, 2015·Annual Review of Genetics·Florian DouamAlexander Ploss

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