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Discovery of Ganoderma lucidum triterpenoids as potential inhibitors against Dengue virus NS2B-NS3 protease.
Sci Rep. 2019 12 13; 9(1):19059.SR

Abstract

Dengue virus (DENV) infection causes serious health problems in humans for which no drug is currently available. Recently, DENV NS2B-NS3 protease has been proposed as a primary target for anti-dengue drug discovery due to its important role in new virus particle formation by conducting DENV polyprotein cleavage. Triterpenoids from the medicinal fungus Ganoderma lucidum have been suggested as pharmacologically bioactive compounds and tested as anti-viral agents against various viral pathogens including human immunodeficiency virus. However, no reports are available concerning the anti-viral activity of triterpenoids from Ganoderma lucidum against DENV. Therefore, we employed a virtual screening approach to predict the functional triterpenoids from Ganoderma lucidum as potential inhibitors of DENV NS2B-NS3 protease, followed by an in vitro assay. From in silico analysis of twenty-two triterpenoids of Ganoderma lucidum, four triterpenoids, viz. Ganodermanontriol (-6.291 kcal/mol), Lucidumol A (-5.993 kcal/mol), Ganoderic acid C2 (-5.948 kcal/mol) and Ganosporeric acid A (-5.983 kcal/mol) were predicted to be viral protease inhibitors by comparison to reference inhibitor 1,8-Dihydroxy-4,5-dinitroanthraquinone (-5.377 kcal/mol). These results were further studied for binding affinity and stability using the molecular mechanics/generalized Born surface area method and Molecular Dynamics simulations, respectively. Also, in vitro viral infection inhibition suggested that Ganodermanontriol is a potent bioactive triterpenoid.

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Authors+Show Affiliations

Bharadwaj S
Department of Biotechnology, Institute of Biotechnology, College of Life and Applied Sciences, Yeungnam University, 280 Daehak-Ro, Gyeongsan, Gyeongbuk, 38541, Republic of Korea.
Lee KE
Department of Biotechnology, Institute of Biotechnology, College of Life and Applied Sciences, Yeungnam University, 280 Daehak-Ro, Gyeongsan, Gyeongbuk, 38541, Republic of Korea.
Dwivedi VD
Centre for Bioinformatics, Computational and Systems Biology, Pathfinder Research and Training Foundation, Greater Noida, India.
Yadava U
Department of Physics, Deen Dayal Upadhyay Gorakhpur University, Gorakhpur, India.
Panwar A
Clinical and Cellular Virology Lab, Translational Health Science and Technology Institute, NCR-Biotech Science Cluster, Faridabad-Gurgaon Highway, Faridabad, 121001, India.
Lucas SJ
Sabanci University Nanotechnology Research and Application Centre (SUNUM), Istanbul, Turkey.
Pandey A
Forest Pathology Division, Forest Research Institute, Dehradun, India.
Kang SG
Department of Biotechnology, Institute of Biotechnology, College of Life and Applied Sciences, Yeungnam University, 280 Daehak-Ro, Gyeongsan, Gyeongbuk, 38541, Republic of Korea. kangsg@ynu.ac.kr.

MeSH

Amino Acid SequenceAntiviral AgentsDengue VirusDrug DiscoveryDrug Evaluation, PreclinicalMolecular Docking SimulationMolecular Dynamics SimulationReishiSerine EndopeptidasesThermodynamicsTriterpenesViral Nonstructural Proteins

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

31836806

Citation

Bharadwaj, Shiv, et al. "Discovery of Ganoderma Lucidum Triterpenoids as Potential Inhibitors Against Dengue Virus NS2B-NS3 Protease." Scientific Reports, vol. 9, no. 1, 2019, p. 19059.
Bharadwaj S, Lee KE, Dwivedi VD, et al. Discovery of Ganoderma lucidum triterpenoids as potential inhibitors against Dengue virus NS2B-NS3 protease. Sci Rep. 2019;9(1):19059.
Bharadwaj, S., Lee, K. E., Dwivedi, V. D., Yadava, U., Panwar, A., Lucas, S. J., Pandey, A., & Kang, S. G. (2019). Discovery of Ganoderma lucidum triterpenoids as potential inhibitors against Dengue virus NS2B-NS3 protease. Scientific Reports, 9(1), 19059. https://doi.org/10.1038/s41598-019-55723-5
Bharadwaj S, et al. Discovery of Ganoderma Lucidum Triterpenoids as Potential Inhibitors Against Dengue Virus NS2B-NS3 Protease. Sci Rep. 2019 12 13;9(1):19059. PubMed PMID: 31836806.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Discovery of Ganoderma lucidum triterpenoids as potential inhibitors against Dengue virus NS2B-NS3 protease. AU - Bharadwaj,Shiv, AU - Lee,Kyung Eun, AU - Dwivedi,Vivek Dhar, AU - Yadava,Umesh, AU - Panwar,Aleksha, AU - Lucas,Stuart J, AU - Pandey,Amit, AU - Kang,Sang Gu, Y1 - 2019/12/13/ PY - 2018/10/18/received PY - 2019/11/30/accepted PY - 2019/12/15/entrez PY - 2019/12/15/pubmed PY - 2020/11/5/medline SP - 19059 EP - 19059 JF - Scientific reports JO - Sci Rep VL - 9 IS - 1 N2 - Dengue virus (DENV) infection causes serious health problems in humans for which no drug is currently available. Recently, DENV NS2B-NS3 protease has been proposed as a primary target for anti-dengue drug discovery due to its important role in new virus particle formation by conducting DENV polyprotein cleavage. Triterpenoids from the medicinal fungus Ganoderma lucidum have been suggested as pharmacologically bioactive compounds and tested as anti-viral agents against various viral pathogens including human immunodeficiency virus. However, no reports are available concerning the anti-viral activity of triterpenoids from Ganoderma lucidum against DENV. Therefore, we employed a virtual screening approach to predict the functional triterpenoids from Ganoderma lucidum as potential inhibitors of DENV NS2B-NS3 protease, followed by an in vitro assay. From in silico analysis of twenty-two triterpenoids of Ganoderma lucidum, four triterpenoids, viz. Ganodermanontriol (-6.291 kcal/mol), Lucidumol A (-5.993 kcal/mol), Ganoderic acid C2 (-5.948 kcal/mol) and Ganosporeric acid A (-5.983 kcal/mol) were predicted to be viral protease inhibitors by comparison to reference inhibitor 1,8-Dihydroxy-4,5-dinitroanthraquinone (-5.377 kcal/mol). These results were further studied for binding affinity and stability using the molecular mechanics/generalized Born surface area method and Molecular Dynamics simulations, respectively. Also, in vitro viral infection inhibition suggested that Ganodermanontriol is a potent bioactive triterpenoid. SN - 2045-2322 UR - https://www.unboundmedicine.com/medline/citation/31836806/Discovery_of_Ganoderma_lucidum_triterpenoids_as_potential_inhibitors_against_Dengue_virus_NS2B_NS3_protease_ DB - PRIME DP - Unbound Medicine ER -