title: Docking studies of Pakistani HCV NS3 helicase: a possible antiviral drug target.
abstract: The nonstructural protein 3 (NS3) of hepatitis C virus (HCV) helicase is believed to be essential for viral replication and has become an attractive target for the development of antiviral drugs. The study of helicase is useful for elucidating its involvement in positive sense single-stranded RNA virus replication and to serve as templates for the design of novel antiviral drugs. In recent years, several models have been proposed on the conformational change leading to protein movement and RNA unwinding. Some compounds have been recently reported to inhibit the helicase and these include small molecules, RNA aptamers and antibodies. The current study is designed to help gain insights for the consideration of potential inhibitors for Pakistani HCV NS3 helicase protein. We have cloned, expressed and purified HCV NS3 helicase from Pakistani HCV serum samples and determined its 3D structure and employed it further in computational docking analysis to identify inhibitors against HCV genotype 3a (GT3a),including six antiviral key molecules such as quercetin, beta-carotene, resveratrol, catechins, lycopene and lutein. The conformation obtained after docking showed good hydrogen bond (HBond) interactions with best docking energy for quercetin and catechins followed by resveratrol and lutein. These anti-helicase key molecules will offer an alternative attraction to target the viral helicase, due to the current limitation with the interferon resistance treatment and presences of high rate of resistance in anti-protease inhibitor classes.
authors.affiliation: IQ Institute of Infection and Immunity, Lahore, Punjab, Pakistan.
authors.forename: Kaneez
authors.initials: K
authors.lastname: Fatima
authors.affiliation: Center of Excellence in Genomic Medicine Research, King Abdul Aziz University, Jeddah, Saudi Arabia.
authors.forename: Shilu
authors.initials: S
authors.lastname: Mathew
authors.affiliation: King Fahd Medical Research Center, King Abdul Aziz University, Jeddah, Saudi Arabia.
authors.forename: Mohd
authors.initials: M
authors.lastname: Suhail
authors.affiliation: King Fahd Medical Research Center, King Abdul Aziz University, Jeddah, Saudi Arabia.
authors.forename: Ashraf
authors.initials: A
authors.lastname: Ali
authors.affiliation: King Fahd Medical Research Center, King Abdul Aziz University, Jeddah, Saudi Arabia.
authors.forename: Ghazi
authors.initials: G
authors.lastname: Damanhouri
authors.affiliation: King Fahd Medical Research Center, King Abdul Aziz University, Jeddah, Saudi Arabia.
authors.forename: Esam
authors.initials: E
authors.lastname: Azhar
authors.affiliation: King Fahd Medical Research Center, King Abdul Aziz University, Jeddah, Saudi Arabia.
authors.forename: Ishtiaq
authors.initials: I
authors.lastname: Qadri
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology; D052157:Aptamers, Nucleotide / Q000737:chemistry / Q000378:metabolism; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects / Q000201:enzymology; D017434:Protein Structure, Tertiary; D012367:RNA, Viral / Q000737:chemistry / Q000378:metabolism; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry*; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D000998:Antiviral Agents; D052157:Aptamers, Nucleotide; D012367:RNA, Viral; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases