Login Register Cart 0
Generic placeholder image

Letters in Drug Design & Discovery

Editor-in-Chief

ISSN (Print): 1570-1808
ISSN (Online): 1875-628X

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

In silico Identification of Potential Small Molecules Targeting Six Proteins in Nipah Virus using Molecular Docking, Pharmacophore and Molecular Dynamics Simulation

Author(s): Arun John, Amitha Joy*, Midhila Padman and P. Praveena

Volume 20, Issue 5, 2023

Published on: 25 August, 2022

Page: [604 - 618] Pages: 15

DOI: 10.2174/1570180819666220616163540

Price: $65

conference banner
Abstract

Introduction: Nipah virus (NiV) is a highly pathogenic zoonotic virus of the genus Henipavirus, which causes severe respiratory illness and deadly encephalitis with a fatality rate of 50%- 70 % in humans. A total of 16 NiV proteins are available in the Protein Data Bank (PDB) of which six proteins belong to the structural class.

Methods: In this study, a cluster of six proteins of classes Viral attachment glycoproteins (2VWD, 2VSM), Fusion glycoprotein (5EVM, 6PD4), Matrix protein (6BK6), and Phosphoprotein (4HEO) were considered as potential therapeutic targets. Here, 25 small molecule inhibitors were chosen, which include 23 natural compounds with antiviral properties and 2 antiviral drug molecules as control. The potential inhibitors among the selected compounds were identified based on docking score, significant intermolecular interactions, ADME (absorption, distribution, metabolism, and excretion) properties, pharmacophore and toxicity studies. Moreover, 100 nanoseconds molecular dynamics simulation was carried out for the best selected compound with all protein targets to understand the stability and binding strength.

Results and Discussion: In this study, we propose that the baicalin was found to be the most potential lead molecule with higher binding affinity, strong bonded interactions, favorable pharmacophore features and higher complex stability.

Conclusion: Hence, the compound identified shall prove effective against the Nipah virus by targeting the viral attachment glycoprotein.

Keywords: Nipah virus, molecular docking, molecular dynamics simulation, toxicity, stability, binding affinity.

« Previous
[1]
Mandell, D. Bennett. Principles and Practice of Infectious Diseases, 8th Edition; , 2015.
[2]
Chattu, V.K.; Kumar, R.; Kumary, S.; Kajal, F.; David, J.K. Nipah virus epidemic in southern India and emphasizing “One Health” approach to ensure global health security. J. Family Med. Prim. Care, 2018, 7(2), 275-283.
[http://dx.doi.org/10.4103/jfmpc.jfmpc_137_18] [PMID: 30090764]
[3]
Soman Pillai, V.; Krishna, G.; Valiya Veettil, M. Nipah Virus: Past outbreaks and future containment. Viruses, 2020, 12(4), 465.
[http://dx.doi.org/10.3390/v12040465] [PMID: 32325930]
[4]
Kamath, J.S.; Hegde, S.; Ajila, V. Nipah Virus: South India in panic mode. Indian J. Occup. Environ. Med., 2018, 22(3), 177-178.
[PMID: 30647521]
[5]
Tigabu, B.; Rasmussen, L.; White, E.L.; Tower, N.; Saeed, M.; Bukreyev, A.; Rockx, B.; LeDuc, J.W.; Noah, J.W.A.A. BSL-4 high-throughput screen identifies sulfonamide inhibitors of Nipah virus. Assay Drug Dev. Technol., 2014, 12(3), 155-161.
[http://dx.doi.org/10.1089/adt.2013.567] [PMID: 24735442]
[6]
Mehand, M.S.; Al-Shorbaji, F.; Millett, P.; Murgue, B. The WHO R&D Blueprint: 2018 review of emerging infectious diseases requiring urgent research and development efforts. Antiviral Res., 2018, 159, 63-67.
[http://dx.doi.org/10.1016/j.antiviral.2018.09.009] [PMID: 30261226]
[7]
Dang, H.V.; Chan, Y.P.; Park, Y.J.; Snijder, J.; Da Silva, S.C.; Vu, B.; Yan, L.; Feng, Y.R.; Rockx, B.; Geisbert, T.W.; Mire, C.E.; Broder, C.C.; Veesler, D. An antibody against the F glycoprotein inhibits Nipah and Hendra virus infections. Nat. Struct. Mol. Biol., 2019, 26(10), 980-987.
[http://dx.doi.org/10.1038/s41594-019-0308-9] [PMID: 31570878]
[8]
Chong, H.T.; Kamarulzaman, A.; Tan, C.T.; Goh, K.J.; Thayaparan, T.; Kunjapan, S.R.; Chew, N.K.; Chua, K.B.; Lam, S.K. Treatment of acute Nipah encephalitis with ribavirin. Ann. Neurol., 2001, 49(6), 810-813.
[http://dx.doi.org/10.1002/ana.1062] [PMID: 11409437]
[9]
Broder, C.C.; Xu, K.; Nikolov, D.B.; Zhu, Z.; Dimitrov, D.S.; Middleton, D.; Pallister, J.; Geisbert, T.W.; Bossart, K.N.; Wang, L.F. A treatment for and vaccine against the deadly Hendra and Nipah viruses. Antiviral Res., 2013, 100(1), 8-13.
[http://dx.doi.org/10.1016/j.antiviral.2013.06.012] [PMID: 23838047]
[10]
Dawes, B.E.; Kalveram, B.; Ikegami, T.; Juelich, T.; Smith, J.K.; Zhang, L.; Park, A.; Lee, B.; Komeno, T.; Furuta, Y.; Freiberg, A.N. Favipiravir (T-705) protects against Nipah virus infection in the hamster model. Sci. Rep., 2018, 8(1), 7604.
[http://dx.doi.org/10.1038/s41598-018-25780-3] [PMID: 29765101]
[11]
Sen, N.; Kanitkar, T.R.; Roy, A.A.; Soni, N.; Amritkar, K.; Supekar, S.; Nair, S.; Singh, G.; Madhusudhan, M.S. Predicting and designing therapeutics against the Nipah virus. PLoS Negl. Trop. Dis., 2019, 13(12), e0007419.
[http://dx.doi.org/10.1371/journal.pntd.0007419] [PMID: 31830030]
[12]
Ali, M.T.; Morshed, M.M.; Hassan, F. A Computational approach for designing a universal epitope-based peptide vaccine against nipah virus. Interdiscip. Sci., 2015, 7(2), 177-185.
[http://dx.doi.org/10.1007/s12539-015-0023-0] [PMID: 26156209]
[13]
Mathieu, C.; Guillaume, V.; Volchkova, V.A.; Pohl, C.; Jacquot, F.; Looi, R.Y.; Wong, K.T.; Legras-Lachuer, C.; Volchkov, V.E.; Lachuer, J.; Horvat, B. Nonstructural Nipah virus C protein regulates both the early host proinflammatory response and viral virulence. J. Virol., 2012, 86(19), 10766-10775.
[http://dx.doi.org/10.1128/JVI.01203-12] [PMID: 22837207]
[14]
Bowden, T.A.; Aricescu, A.R.; Gilbert, R.J.; Grimes, J.M.; Jones, E.Y.; Stuart, D.I. Structural basis of Nipah and Hendra virus attachment to their cell-surface receptor ephrin-B2. Nat. Struct. Mol. Biol., 2008, 15(6), 567-572.
[http://dx.doi.org/10.1038/nsmb.1435] [PMID: 18488039]
[15]
Communie, G.; Habchi, J.; Yabukarski, F.; Blocquel, D.; Schneider, R.; Tarbouriech, N.; Papageorgiou, N.; Ruigrok, R.W.H.; Jamin, M.; Jensen, M.R.; Longhi, S.; Blackledge, M. Atomic resolution description of the interaction between the nucleoprotein and phosphoprotein of Hendra virus. PLoS Pathog., 2013, 9(9), e1003631.
[http://dx.doi.org/10.1371/journal.ppat.1003631] [PMID: 24086133]
[16]
Liu, Y.C.; Grusovin, J.; Adams, T.E. Electrostatic interactions between hendra virus matrix proteins are required for efficient virus-like-particle assembly. J. Virol., 2018, 92(13), e00143-e18.
[http://dx.doi.org/10.1128/JVI.00143-18] [PMID: 29695428]
[17]
Atanasov, A.G.; Zotchev, S.B.; Dirsch, V.M.; Supuran, C.T. Natural products in drug discovery: advances and opportunities. Nat. Rev. Drug Discov., 2021, 20(3), 200-216.
[http://dx.doi.org/10.1038/s41573-020-00114-z] [PMID: 33510482]
[18]
Sun, Z.G.; Zhao, T.T.; Lu, N.; Yang, Y.A.; Zhu, H.L. Research progress of glycyrrhizic acid on antiviral activity. Mini Rev. Med. Chem., 2019, 19(10), 826-832.
[http://dx.doi.org/10.2174/1389557519666190119111125] [PMID: 30659537]
[19]
Kuo, Y.C.; Lin, L.C.; Tsai, W.J.; Chou, C.J.; Kung, S.H.; Ho, Y.H. Samarangenin B from Limonium sinense suppresses herpes simplex virus type 1 replication in Vero cells by regulation of viral macromolecular synthesis. Antimicrob. Agents Chemother., 2002, 46(9), 2854-2864.
[http://dx.doi.org/10.1128/AAC.46.9.2854-2864.2002] [PMID: 12183238]
[20]
Adianti, M.; Aoki, C.; Komoto, M.; Deng, L.; Shoji, I.; Wahyuni, T.S.; Lusida, M.I. Soetjipto, Fuchino. H.; Kawahara, N. Hotta H. Anti-hepatitis C virus compounds obtained from Glycyrrhizauralensis and other Glycyrrhiza species. Microbiol. Immunol., 2014, 58(3), 180-187.
[http://dx.doi.org/10.1111/1348-0421.12127] [PMID: 24397541]
[21]
Gu, R.; Dou, G.; Wang, J.; Dong, J.; Meng, Z. Simultaneous determination of 1,5-dicaffeoylquinic acid and its active metabolites in human plasma by liquid chromatography-tandem mass spectrometry for pharmacokinetic studies. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2007, 852(1-2), 85-91.
[http://dx.doi.org/10.1016/j.jchromb.2006.12.055] [PMID: 17267301]
[22]
Zandi, K.; Lani, R.; Wong, P-F.; Teoh, B-T.; Sam, S-S.; Johari, J.; Mustafa, M.R.; AbuBakar, S. Flavone enhances dengue virus type-2 (NGC strain) infectivity and replication in vero cells. Molecules, 2012, 17(3), 2437-2445.
[http://dx.doi.org/10.3390/molecules17032437] [PMID: 22374315]
[23]
Wang, Q.; Zhu, N.; Hu, J.; Wang, Y.; Xu, J.; Gu, Q.; Lieberman, P.M.; Yuan, Y. The mTOR inhibitor manassantin B reveals a crucial role of mTORC2 signaling in Epstein-Barr virus reactivation. J. Biol. Chem., 2020, 295(21), 7431-7441.
[http://dx.doi.org/10.1074/jbc.RA120.012645] [PMID: 32312752]
[24]
Mori, M.; Ciaco, S.; Mély, Y.; Karioti, A. Inhibitory effect of lithospermic acid on the HIV-1 nucleocapsid protein. Molecules, 2020, 25(22), 5434.
[http://dx.doi.org/10.3390/molecules25225434] [PMID: 33233563]
[25]
Mukherjee, R.; Kumar, V.; Srivastava, S.K.; Agarwal, S.K.; Burman, A.C. Betulinic acid derivatives as anticancer agents: structure activity relationship. Anticancer. Agents Med. Chem., 2006, 6(3), 271-279.
[http://dx.doi.org/10.2174/187152006776930846] [PMID: 16712455]
[26]
Liedtke, M.D.; Rathbun, R.C. Warfarin-antiretroviral interactions. Ann. Pharmacother., 2009, 43(2), 322-328.
[http://dx.doi.org/10.1345/aph.1L497] [PMID: 19196837]
[27]
Loya, S.; Rudi, A.; Kashman, Y.; Hizi, A. Polycitone A, a novel and potent general inhibitor of retroviral reverse transcriptases and cellular DNA polymerases. Biochem. J., 1999, 344(Pt 1), 85-92.
[http://dx.doi.org/10.1042/bj3440085] [PMID: 10548537]
[28]
Wang, L.; Yang, R.; Yuan, B.; Liu, Y.; Liu, C. The antiviral and antimicrobial activities of licorice, a widely-used Chinese herb. Acta Pharm. Sin. B, 2015, 5(4), 310-315.
[http://dx.doi.org/10.1016/j.apsb.2015.05.005] [PMID: 26579460]
[29]
Wu, W.; Li, R.; Li, X.; He, J.; Jiang, S.; Liu, S.; Yang, J. Quercetin as an antiviral agent inhibits influenza A virus (IAV) entry. Viruses, 2015, 8(1), 6.
[http://dx.doi.org/10.3390/v8010006] [PMID: 26712783]
[30]
Mounce, B.C.; Cesaro, T.; Carrau, L.; Vallet, T.; Vignuzzi, M. Curcumin inhibits Zika and chikungunya virus infection by inhibiting cell binding. Antiviral Res., 2017, 142, 148-157.
[http://dx.doi.org/10.1016/j.antiviral.2017.03.014] [PMID: 28343845]
[31]
Huang, T.J.; Tsai, Y.C.; Chiang, S.Y.; Wang, G.J.; Kuo, Y.C.; Chang, Y.C.; Wu, Y.Y.; Wu, Y.C. Anti-viral effect of a compound isolated from Liriope platyphylla against hepatitis B virus in vitro. Virus Res., 2014, 192, 16-24.
[http://dx.doi.org/10.1016/j.virusres.2014.07.015] [PMID: 25150190]
[32]
Nagai, T.; Suzuki, Y.; Tomimori, T.; Yamada, H. Antiviral activity of plant flavonoid, 5,7,4′-trihydroxy-8-methoxyflavone, from the roots of Scutellaria baicalensis against influenza A (H3N2) and B viruses. Biol. Pharm. Bull., 1995, 18(2), 295-299.
[http://dx.doi.org/10.1248/bpb.18.295] [PMID: 7742801]
[33]
Chuanasa, T.; Phromjai, J.; Lipipun, V.; Likhitwitayawuid, K.; Suzuki, M.; Pramyothin, P.; Hattori, M.; Shiraki, K. Anti-herpes simplex virus (HSV-1) activity of oxyresveratrol derived from Thai medicinal plant: mechanism of action and therapeutic efficacy on cutaneous HSV-1 infection in mice. Antiviral Res., 2008, 80(1), 62-70.
[http://dx.doi.org/10.1016/j.antiviral.2008.05.002] [PMID: 18565600]
[34]
Sudo, K.; Konno, K.; Shigeta, S.; Yokota, T. Inhibitory effects of podophyllotoxin derivatives on Herpes simplex virus replication. Antivir. Chem. Chemother., 1998, 9(3), 263-267.
[http://dx.doi.org/10.1177/095632029800900307] [PMID: 9875405]
[35]
Tang, K.; He, S.; Zhang, X.; Guo, J.; Chen, Q.; Yan, F.; Banadyga, L.; Zhu, W.; Qiu, X.; Guo, Y. Tangeretin, an extract from Citrus peels, blocks cellular entry of arenaviruses that cause viral hemorrhagic fever. Antiviral Res., 2018, 160, 87-93.
[http://dx.doi.org/10.1016/j.antiviral.2018.10.011] [PMID: 30339847]
[36]
Lin, S.C.; Chen, M.C.; Li, S.; Lin, C.C.; Wang, T.T. Antiviral activity of nobiletin against chikungunya virus in vitro. Antivir. Ther., 2017, 22(8), 689-697.
[http://dx.doi.org/10.3851/IMP3167] [PMID: 28406093]
[37]
Hua, Y.C.; Chien, M.Y.; Ta, C.L.L. T. L.; Lien, C. C.; Chun, C. L. Excoecarianin isolated from Phyllanthus urinaria Linnea, inhibits Herpes Simplex Virus Type 2 infection through inactivation of viral particles. Evid. Based Complement. Alternat. Med., 2011, 2011, 259103.
[38]
Wahyuni, T.S.; Widyawaruyanti, A.; Lusida, M.I.; Fuad, A. Soetjipto.; Fuchino, H.; Kawahara N.; Hayashi, Y.; Aoki, C.; Hotta, H. Inhibition of hepatitis C virus replication by chalepin and pseudane IX isolated from Rutaangustifolia leaves. Fitoterapia, 2014, 99, 276-283.
[http://dx.doi.org/10.1016/j.fitote.2014.10.011] [PMID: 25454460]
[39]
Hayashi, K.; Niwayama, S.; Hayashi, T.; Nago, R.; Ochiai, H.; Morita, N. In vitro and in vivo antiviral activity of scopadulcic acid B from Scoparia dulcis, Scrophulariaceae, against herpes simplex virus type 1. Antiviral Res., 1988, 9(6), 345-354.
[http://dx.doi.org/10.1016/0166-3542(88)90036-8] [PMID: 2852487]
[40]
Samdani, A.; Vetrivel, U. POAP: A GNU parallel based multithreaded pipeline of open babel and AutoDock suite for boosted high throughput virtual screening. Comput. Biol. Chem., 2018, 74, 39-48.
[http://dx.doi.org/10.1016/j.compbiolchem.2018.02.012] [PMID: 29533817]
[41]
Lagorce, D.; Sperandio, O.; Galons, H.; Miteva, M.A.; Villoutreix, B.O. FAF-Drugs2: free ADME/tox filtering tool to assist drug discovery and chemical biology projects. BMC Bioinformatics, 2008, 9(1), 396.
[http://dx.doi.org/10.1186/1471-2105-9-396] [PMID: 18816385]
[42]
Desmond Molecular Dynamics System. D. E. Shaw Research, New York, NY, 2021. Maestro-DesmonFAF-Drugs2 : a free ADME/tox filtering tool to assist drug discovery and chemical biology. , 2021.
[43]
Xu, K.; Chan, Y.P.; Bradel-Tretheway, B.; Akyol-Ataman, Z.; Zhu, Y.; Dutta, S.; Yan, L.; Feng, Y.; Wang, L.F.; Skiniotis, G.; Lee, B.; Zhou, Z.H.; Broder, C.C.; Aguilar, H.C.; Nikolov, D.B. Crystal structure of the pre-fusion nipah virus fusion glycoprotein reveals a novel hexamer-of-trimers assembly. PLoS Pathog., 2015, 11(12), e1005322.
[http://dx.doi.org/10.1371/journal.ppat.1005322] [PMID: 26646856]
[44]
Xu, K.; Chan, Y.P.; Rajashankar, K.R.; Khetawat, D.; Yan, L.; Kolev, M.V.; Broder, C.C.; Nikolov, D.B. New insights into the Hendra virus attachment and entry process from structures of the virus G glycoprotein and its complex with Ephrin-B2. PLoS One, 2012, 7(11), e48742.
[http://dx.doi.org/10.1371/journal.pone.0048742] [PMID: 23144952]
[45]
Wolber, G.; Langer, T. LigandScout: 3-D pharmacophores derived from protein-bound ligands and their use as virtual screening filters. J. Chem. Inf. Model., 2005, 45(1), 160-169.
[http://dx.doi.org/10.1021/ci049885e] [PMID: 15667141]

Rights & Permissions Print Cite
Article Metrics
28
3
Wayfinder Image
© 2024 Bentham Science Publishers | Privacy Policy