Chikungunya protease domain-high throughput virtual screening
Autor(es): Jadav, Surender Singh; Jayaprakash, Venkatesan; Basu, Arijit;Sinha, Barij Nayan
Resumo: Chikungunya viras (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 drag design against Chikungunya nSP2 protease (PDB: 3TRK). Highthroughput virtual screening of publicly available databases, ZINC 12 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.
Palavras-Chave: Screening; Computer programs; Disease control; Metabolites; Pest control; Vaccines; Aquatic insects; Mortality causes; Public health; Aedes aegypti; Aedes albopictus
Imprenta: Proceedings of World Academy of Science, Engineering and Technology, v.6, n. 12, p. 718-721, 2012.
Descritores: Aedes aegypti - Vaccine ; Aedes aegypti - Public health
Data de publicação: 2012
