{"title":"Chikungunya Protease Domain\u2013High Throughput Virtual Screening","authors":"Surender Singh Jadav, Venkatesan Jayaprakash, Arijit Basu, Barij Nayan Sinha","volume":72,"journal":"International Journal of Pharmacological and Pharmaceutical Sciences","pagesStart":718,"pagesEnd":728,"ISSN":"1307-6892","URL":"https:\/\/publications.waset.org\/pdf\/14462","abstract":"
Chikungunya virus (CHICKV) is an arboviruses belonging to family Tagoviridae and is transmitted to human through by mosquito (Aedes aegypti and Aedes albopictus) bite. A large outbreak of chikungunya has been reported in India between 2006 and 2007, along with several other countries from South-East Asia and for the first time in Europe. It was for the first time that the CHICKV outbreak has been reported with mortality from Reunion Island and increased mortality from Asian countries. CHICKV affects all age groups, and currently there are no specific drugs or vaccine to cure the disease. The need of antiviral agents for the treatment of CHICKV infection and the success of virtual screening against many therapeutically valuable targets led us to carry out the structure based drug design against Chikungunya nSP2 protease (PDB: 3TRK). Highthroughput virtual screening of publicly available databases, ZINC12 and BindingDB, has been carried out using the Openeye tools and Schrodinger LLC software packages. Openeye Filter program has been used to filter the database and the filtered outputs were docked using HTVS protocol implemented in GLIDE package of Schrodinger LLC. The top HITS were further used for enriching the similar molecules from the database through vROCS; a shape based screening protocol implemented in Openeye. The approach adopted has provided different scaffolds as HITS against CHICKV protease. Three scaffolds: Indole, Pyrazole and Sulphone derivatives were selected based on the docking score and synthetic feasibility. Derivatives of Pyrazole were synthesized and submitted for antiviral screening against CHICKV.<\/p>\r\n","references":"[1] Aida, I., \"Numerical Computation of a Tsunami Based on a Fault Origin\r\nModel of an Earthquake\", J. Seismol. Soc. Japan, 27, 141-154, 1974.\r\n[2] Ammon, C. J., Ji, C., Thio, H.-K., Robinson, D., Ni, S., Hjorleifsdottir,\r\nV., Kanamori, H., Lay, T., Das, S., Helmberger, D., Ichinose, G., Polet,\r\nJ. & Wald, D., \"Rupture Process of the 2004 Sumatra-Andaman\r\nEarthquake\", Science, 308(5725), 1133 - 1139, 2005.\r\n[3] Arreaga-Vargas, P., Ortiz, M. & Farreras, S.F., \"Mapping the Possible\r\nTsunami Hazard as the First Step Towards a Tsunami Resistant\r\nCommunity in Esmeraldas, Ecuador. In K. Satake (Ed.), Tsunamis: Case\r\nStudies and Recent Developments (pp. 203 - 215). Netherlands:\r\nSpringer, 2005.\r\n[4] Cho, Y.-S., Jin, S.-B., & Lee, H.-J.,\"Safety analysis of Ulchin Nuclear\r\nPower Plant against Nihonkai-Chubu Earthquake Tsunami\", Nuclear\r\nEngineering and Design, 228(1-3), 393-400, 2004.\r\n[5] Dube, S. K., Sinha, P.C., & Roy, G.D. , \"The Effect of a Continuously\r\nDeforming Coastline on the Numerical Simulation of Storm Surge in\r\nBangladesh\", Mathematics and Computers in Simulation, 28, 41 - 56,\r\n1986.\r\n[6] Inan, A., & Balas, L. A, \"Moving Boundary Wave Run-Up Model. In Y.\r\nShi, Albada, G.D.v., Dongarra\", J., & Sloot, P.M.A. (Ed.),\r\nComputational Science - ICCS (pp. 38-45). Berlin \/ Heidelberg:\r\nSpringer, 2007.\r\n[7] Karim, M. F., Roy, G.D., Ismail, A.I.M., & Meah, M.A. , \"A Shallow\r\nWater Model for Computing Tsunami along the West Coast of\r\nPeninsular Malaysia and Thailand Using Boundary-Fitted Curvilinear\r\nGrids\" Science of Tsunami Hazards, 26(1), 21 - 41, 2007.\r\n[8] Kowalik, Z., Knight, W., & Whitmore, P. M.., \"Numerical Modeling of\r\nthe Tsunami: Indonesian Tsunami of 26 December 2004\",Sc. Tsunami\r\nHazards, 23(1), 40 - 56, 2005.\r\n[9] Lynch, F. R., & Gray, W.G., \"Finite Element Simulation of Flow in\r\nDeforming Regions, 1980. J. Comput. Phys., 36, 135 - 153, 1980.\r\n[10] Okada, Y., \"Surface Deformation due to Shear and Tensile Faults in a\r\nHalf Space\", Bull, Seism. Soc. Am., 75, 1135 - 1154, 1985.\r\n[11] Papadopoulos, G. A., Caputo, R., McAdoo, B., Pavlides, S., Karastathis,\r\nV., Fokaefs, A., Orfanogiannaki, K. & Valkaniotis, S.,\" The large\r\ntsunami of 26 December 2004: Field observations and eyewitnesses\r\naccounts from Sri Lanka, Maldives Is. and Thailand\", Earth Planets\r\nSpace, 58, 233 - 241, 2006.\r\n[12] Roy, G. D., Karim, M. F., & Ismail, A. M., \"A 1-D Shallow Water\r\nModel for Computing Inland Inundation due to Long Waves Using a\r\nMoving Boundary\", Far East J. Appl. Math., 28(3), 395 - 408, 2007.\r\n[13] Tanioka, Y., Yudhicara, Kususose, T., Kathiroli, S., Nishimura, Y.,\r\nIwasaki, S. & Satake, K. \"Rapture process of 2004 great Sumatra-\r\nAndaman earthquake estimated from tsunami waveforms,\" Earth Planets\r\nSpace, 58, 203 - 209, 2006.\r\n[14] Viana-Baptista, M. A., Soares, P.M., Miranda, J.M. & Luis, J.F.,\r\n\"Tsunami Propagation along Tagus Estuary (Lisbon, Portugal)\r\nPreliminary Results\", Science of Tsunami Hazards, 24(5), 329 - 338,\r\n2006.\r\n[15] Wijetunge, J. J., \"Tsunami on 26 December 2004: Spatial distribution of\r\ntsunami height and the extent of inundation in Sri-Lanka, Science of\r\nTsunami Hazard, 24(3) 225-239, 2006.","publisher":"World Academy of Science, Engineering and Technology","index":"Open Science Index 72, 2012"}