Development of small-molecule viral inhibitors targeting various stages of the life cycle of emerging and re-emerging viruses

Abstract

In recent years, unexpected outbreaks of infectious diseases caused by emerging and re-emerging viruses have become more frequent, which is possibly due to environmental changes. These outbreaks result in the loss of life and economic hardship. Vaccines and therapeutics should be developed for the prevention and treatment of infectious diseases. In this review, we summarize and discuss the latest progress in the development of small-molecule viral inhibitors against highly pathogenic coronaviruses, including severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus, Ebola virus, and Zika virus. These viruses can interfere with the specific steps of viral life cycle by blocking the binding between virus and host cells, disrupting viral endocytosis, disturbing membrane fusion, and interrupting viral RNA replication and translation, thereby demonstrating potent therapeutic effect against various emerging and re-emerging viruses. We also discuss some general strategies for developing small-molecule viral inhibitors.

Keywords

emerging and re-emerging viruses / small-molecule inhibitor / coronavirus / Ebola virus / Zika virus / life cycle

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Acknowledgements

This work was supported by grants from the Shanghai Public Health Clinical Center (Nos. 2016-27 and KY-GW-2017-17), the National Key Research and Development Program of China (Nos. 2016YFC1201000 and 2016YFC1200405 to S. J., 2016YFC-1202901 to L. L.), the Sanming Project of Medicine in Shenzhen to L. L. and S. J., and the Hi-Tech Research and Development Program of China (863 Program) (No. 2015AA020930 to L. L.). We also thank Guangzhou Sagene Biotech Co., Ltd. for its aid in the preparation of the figures.

Compliance with ethics guidelines

Xiaohuan Wang, Peng Zou, Fan Wu, Lu Lu, and Shibo Jiang declare no conflict of interest. This manuscript is a review article. It does not involve a research protocol requiring approval by relevant institutional review board or ethics committee.

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2017 Higher Education Press and Springer-Verlag GmbH Germany