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Cited by 390

The DOI matches its Crossref record; 14 of the 14 references it cites were found in a registry or an index.

An adenosine nucleoside inhibitor of dengue virus

Open access
Yin, Zheng, Chen, Yen-Liang, Schul, Wouter, Wang, Qing-Yin, Gu, Feng, Duraiswamy, Jeyaraj, Kondreddi, Ravinder Reddy, Niyomrattanakit, Pornwaratt, Lakshminarayana, Suresh B., Goh, Anne, Xu, Hao Ying, Liu, Wei, Liu, Boping, Lim, Joanne Y. H., Ng, Chuan Young, Qing, Min, Lim, Chin Chin, Yip, Andy, Wang, Gang, Chan, Wai Ling, Tan, Hui Pen, Lin, Kai, Zhang, Bo, Zou, Gang, Bernard, Kristen A., Garrett, Christine, Beltz, Karen, Dong, Min, Weaver, Margaret, He, Handan, Pichota, Arkadius, Dartois, Veronique, Keller, Thomas H., Shi, Pei-Yong·2009·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.0907010106
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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 when rats were orally dosed with NITD008 at 50 mg/kg daily for 1 week. However, NOAEL could not be accomplished when rats and dogs were dosed daily for 2 weeks. Nevertheless, our results have proved the concept that a nucleoside inhibitor could be developed for potential treatment of flavivirus infections.

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Metadata

Authors
Yin, Z., Chen, Y.-L., Schul, W., Wang, Q.-Y., Gu, F., Duraiswamy, J., Kondreddi, R. R., Niyomrattanakit, P., Lakshminarayana, S. B., Goh, A., Xu, H. Y., Liu, W., Liu, B., Lim, J. Y. H., Ng, C. Y., Qing, M., Lim, C. C., Yip, A., Wang, G., Chan, W. L., Tan, H. P., Lin, K., Zhang, B., Zou, G., Bernard, K. A., Garrett, C., Beltz, K., Dong, M., Weaver, M., He, H., Pichota, A., Dartois, V., Keller, T. H., & Shi, P.-Y.
Venue
Proceedings of the National Academy of Sciences
Publisher
Proceedings of the National Academy of Sciences
Published
2009-12
Volume
106
Issue
48
Pages
20435-20439
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.0907010106
OpenAlex
W1981910825
Cited by
390
References
14
FWCI
16.06
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: An adenosine nucleoside inhibitor of dengue virus. https://app.cochat.ai/papers/10.1073/pnas.0907010106
The paper
Yin, Z., Chen, Y.-L., Schul, W., Wang, Q.-Y., Gu, F., Duraiswamy, J., Kondreddi, R. R., Niyomrattanakit, P., Lakshminarayana, S. B., Goh, A., Xu, H. Y., Liu, W., Liu, B., Lim, J. Y. H., Ng, C. Y., Qing, M., Lim, C. C., Yip, A., Wang, G., . . . Shi, P.-Y. (2009). An adenosine nucleoside inhibitor of dengue virus. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0907010106

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.