A Novel Benzoxazole Inhibitor of Dengue Virus Replication that 1 Targets the NS 3 Helicase
نویسندگان
چکیده
A Novel Benzoxazole Inhibitor of Dengue Virus Replication that 1 Targets the NS3 Helicase 2 3 Chelsea M. Byrd*, Douglas W. Grosenbach, Aklile Berhanu, Dongcheng Dai, 4 Kevin F. Jones, Kara B. Cardwell, Christine Schneider,Guang Yang, 5 Shanthakumar Tyavanagimatt, Chris Harver, Kristin A. Wineinger, Jessica Page, 6 Eric Stavale, Melialani A. Stone, Kathleen P. Fuller, Candace Lovejoy, 7 Janet M. Leeds, Dennis E. Hruby, and Robert Jordan 8 9 SIGA Technologies, Inc., Corvallis, OR 97333 10 +Current address: Roche R&D Center, Shanghai, China 11 ++Current address: Gilead Sciences, Inc., Foster City, CA 94404 12 13 *Corresponding Author: Mailing Address: 4575 SW Research Way, Corvallis, OR 14 97333. Phone: 541-753-2000. Fax: 541-753-9999. E-mail: [email protected] 15 16 Running Title: A dengue virus helicase inhibitor 17 18
منابع مشابه
Targeting Dengue Virus NS-3 Helicase by Ligand based Pharmacophore Modeling and Structure based Virtual Screening
Dengue fever is an emerging public health concern, with several million viral infections occur annually, for which no effective therapy currently exist. Non-structural protein 3 (NS-3) Helicase encoded by the dengue virus (DENV) is considered as a potential drug target to design new and effective drugs against dengue. Helicase is involved in unwinding of dengue RNA. This study was conducted to ...
متن کاملIvermectin is a potent inhibitor of flavivirus replication specifically targeting NS3 helicase activity: new prospects for an old drug.
OBJECTIVES Infection with yellow fever virus (YFV), the prototypic mosquito-borne flavivirus, causes severe febrile disease with haemorrhage, multi-organ failure and a high mortality. Moreover, in recent years the Flavivirus genus has gained further attention due to re-emergence and increasing incidence of West Nile, dengue and Japanese encephalitis viruses. Potent and safe antivirals are urgen...
متن کاملIdentification and Biochemical Characterization of Halisulfate 3 and Suvanine as Novel Inhibitors of Hepatitis C Virus NS3 Helicase from a Marine Sponge
Hepatitis C virus (HCV) is an important etiological agent that is responsible for the development of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. HCV nonstructural protein 3 (NS3) helicase is a possible target for novel drug development due to its essential role in viral replication. In this study, we identified halisulfate 3 (hal3) and suvanine as novel NS3 helicase inhibi...
متن کاملNS3 protease from flavivirus as a target for designing antiviral inhibitors against dengue virus
The development of novel therapeutic agents is essential for combating the increasing number of cases of dengue fever in endemic countries and among a large number of travelers from non-endemic countries. The dengue virus has three structural proteins and seven non-structural (NS) proteins. NS3 is a multifunctional protein with an N-terminal protease domain (NS3pro) that is responsible for prot...
متن کاملNS3 helicase from dengue virus specifically recognizes viral RNA sequence to ensure optimal replication
The protein-RNA interactions within the flavivirus replication complex (RC) are not fully understood. Our structure of dengue virus NS3 adenosine triphosphatase (ATPase)/helicase bound to the conserved 5' genomic RNA 5'-AGUUGUUAGUCU-3' reveals that D290 and R538 make specific interactions with G2 and G5 bases respectively. We show that single-stranded 12-mer RNA stimulates ATPase activity of NS...
متن کامل