magazinelogo

International Journal of Clinical and Experimental Medicine Research

ISSN Print: 2575-7989 Downloads: 183727 Total View: 2281099
Frequency: quarterly ISSN Online: 2575-7970 CODEN: IJCEMH
Email: ijcemr@hillpublisher.com
Article Open Access http://dx.doi.org/10.26855/ijcemr.2022.10.012

Virtual Screening: Small Molecular Inhibitors of Human Norovirus RNA-dependent RNA-polymerase

Lufei Liu

Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, China.

*Corresponding author: Lufei Liu

Published: November 15,2022

Abstract

Noroviruses, belonging to the family of Caliciviridae, are non-enveloped RNA viruses with single strands that cause illnesses such as acute gastroenteritis. Every year, it can bring about 685 million acute gastroenteritis cases, which leads to a serious situation for medical care. About one-third of patients are children under 5 years old. Even more dangerous, especially in developing countries, five thousand kids die every year. Currently, there is no specific medicine to treat human norovirus yet. Vaccine treatments and potential drugs are still in clinical trials and are not available yet. To prevent the outbreak of human norovirus, inhibiting the replication of viral genomes can be a suitable treatment method. Since RNA-dependent RNA-polymerase (RdRp) plays an important role during crucial steps of viral replication and is highly conserved during the amplification of RNA viruses, this protein can be a prospective target for selecting future anti-viral drugs. In this context, eleven small molecular compounds (drugs) are selected during the process of blind docking using Auto Dock Vina and tested in vitro experiments as potential human norovirus inhibitors. The enzyme activity is tested in experiments in vitro, indicating the inhibitory activities of these small molecular compounds.

References

[1] Alhatlani, B., Vashist, S., and Goodfellow, I. (2015). Functions of the 5’ and3’-ends of calicivirus genomes. Virus Res. 206, 134-143.

[2] Cen, S., Li, Q., & Yi, D. (2020). Application of Emtraitinib in the Preparation of Viral Inhibitors. CN111544434A.

[3] Centers for Disease Control and Prevention. (2021, March 5). Norovirus worldwide. Centers for Disease Control and Prevention. Retrieved June 13, 2022, from https://www.cdc.gov/norovirus/trends-outbreaks/worldwide.html. 

[4] Centers for Disease Control and Prevention. (2021, March 5). Norovirus virus classification. Centers for Disease Control and Prevention. Retrieved June 12, 2022, from https://www.cdc.gov/norovirus/lab/virus-classification.html.

[5] Centers for Disease Control and Prevention. (2021, March 5). How you treat norovirus. Centers for Disease Control and Prevention. Retrieved June 12, 2022, from https://www.cdc.gov/norovirus/about/treatment.html.

[6] Mattison, C. P., Cardemil, C. V., & Hall, A. J. (2018). Progress on norovirus vaccine research: public health considerations and future directions. Expert review of vaccines, 17(9), 773-784. https://doi.org/10.1080/14760584.2018.1510327.

[7] Trott, Oleg, and Arthur J. Olson. “Autodock Vina: Improving the Speed and Accuracy of Docking with a New Scoring Function, Efficient Optimization, and Multithreading.” Journal of Computational Chemistry, 2009, https://doi.org/10.1002/jcc.21334. 

[8] Tarantino, D., Pezzullo, M., Mastrangelo, E., Croci, R., Rohayem, J., Robel, I., Bolognesi, M., & Milani, M. (2014). Naphthalene-sulfonate inhibitors of human norovirus RNA-dependent RNA-polymerase. Antiviral Research, 102, 23-28. https://doi.org/10.1016/j.antiviral.2013.11.016.

[9] Pierce™ BCA Protein Assay Kit. Thermo Fisher Scientific - US. (n.d.). Retrieved June 12, 2022, from 

https://www.thermofisher.com/order/catalog/product/23225.

[10] Singer, V. L., Jones, L. J., Yue, S. T., & Haugland, R. P. (1997). Characterization of PicoGreen reagent and development of a fluorescence-based solution assay for double-stranded DNA quantitation. Analytical Biochemistry, 249(2), 228-238. https://doi.org/10.1006/abio.1997.2177.

[11] Shimoike, T., Hayashi, T., Oka, T., & Muramatsu, M. (2021). The predicted stem-loop structure in the 3'-end of the human norovirus antigenomic sequence is required for its genomic RNA synthesis by its RdRp. The Journal of biological chemistry, 297(4), 101225. https://doi.org/10.1016/j.jbc.2021.101225.

[12] Sebaugh J. L. (2011). Guidelines for accurate EC50/IC50 estimation. Pharmaceutical statistics, 10(2), 128-134. 

https://doi.org/10.1002/pst.426.

[13] Prinz, H. (2009). Hill coefficients, dose–response curves and allosteric mechanisms. Journal of Chemical Biology, 3(1), 37-44. https://doi.org/10.1007/s12154-009-0029-3.

[14] Kumaraswamy, S., & Tobias, R. (2015). Label-free kinetic analysis of an antibody-antigen interaction using biolayer interferometry. Methods in molecular biology (Clifton, N.J.), 1278, 165-182. https://doi.org/10.1007/978-1-4939-2425-7_10.

[15] Mastrangelo, E., Pezzullo, M., Tarantino, D., Petazzi, R., Germani, F., Kramer, D., Robel, I., Rohayem, J., Bolognesi, M., & Milani, M. (2012). Structure-based inhibition of Norovirus RNA-dependent RNA polymerases. Journal of molecular biology, 419(3-4), 198-210. https://doi.org/10.1016/j.jmb.2012.03.008.

How to cite this paper

Virtual Screening: Small Molecular Inhibitors of Human Norovirus RNA-dependent RNA-polymerase

How to cite this paper: Lufei Liu. (2022) Virtual Screening: Small Molecular Inhibitors of Human Norovirus RNA-dependent RNA-polymerase. International Journal of Clinical and Experimental Medicine Research6(4), 392-401.

DOI: http://dx.doi.org/10.26855/ijcemr.2022.10.012