Presentation Title

Synthesis of Arginine Mimetics for the Inhibition of the NS2B-NS3 Protease

Faculty Mentor

Dr. Nicholas Salzameda

Start Date

18-11-2017 10:00 AM

End Date

18-11-2017 11:00 AM

Location

BSC-Ursa Minor 114

Session

Poster 1

Type of Presentation

Poster

Subject Area

physical_mathematical_sciences

Abstract

Synthesis of Arginine Mimetics for the Inhibition of the NS2B-NS3 Protease

West Nile Virus (WNV) is a common illness spread to humans by infected mosquitos, which has caused a global epidemic due to the feeding cycle of infected mosquito carriers. With millions of people infected yearly about 1% of them will develop a fatal neurological condition. Presently, there are no vaccines or therapeutic methods to treat WNV infections. Thus, mosquito control is the most viable option for lowering WNV infections.

The WNV is a flavivirus which contains a positive single stranded RNA and a viral envelope. The RNA will then be translated by the host cell to produce three structural and seven non-structural peptides. The translation of this polyprotein is vital to produce progeny virions and their eventual exit of the host cell. The NS2B-NS3 protease is part of the genome responsible for the virus’s replication. Inhibiting the NS2B-NS3protease would drastically affect WNV replication. The development of small molecule NS2B-NS3 protease inhibitors would restrict the genomic replication process preventing further replication. The NS2B-NS3 protease active site has a disposition to bind positive charged amino acid arginine.

Using organic synthesis our laboratory is creating heterocyclic arginine mimetics. The goal is to create better inhibitors for the NS2B-NS3 protease by mimicking arginine and binding tightly to the active site. These mimetic structures will be attached to different molecules via a free amine. The molecules will then be tested in competitive enzyme assays for the WNV NS2B-NS3 protease.

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Nov 18th, 10:00 AM Nov 18th, 11:00 AM

Synthesis of Arginine Mimetics for the Inhibition of the NS2B-NS3 Protease

BSC-Ursa Minor 114

Synthesis of Arginine Mimetics for the Inhibition of the NS2B-NS3 Protease

West Nile Virus (WNV) is a common illness spread to humans by infected mosquitos, which has caused a global epidemic due to the feeding cycle of infected mosquito carriers. With millions of people infected yearly about 1% of them will develop a fatal neurological condition. Presently, there are no vaccines or therapeutic methods to treat WNV infections. Thus, mosquito control is the most viable option for lowering WNV infections.

The WNV is a flavivirus which contains a positive single stranded RNA and a viral envelope. The RNA will then be translated by the host cell to produce three structural and seven non-structural peptides. The translation of this polyprotein is vital to produce progeny virions and their eventual exit of the host cell. The NS2B-NS3 protease is part of the genome responsible for the virus’s replication. Inhibiting the NS2B-NS3protease would drastically affect WNV replication. The development of small molecule NS2B-NS3 protease inhibitors would restrict the genomic replication process preventing further replication. The NS2B-NS3 protease active site has a disposition to bind positive charged amino acid arginine.

Using organic synthesis our laboratory is creating heterocyclic arginine mimetics. The goal is to create better inhibitors for the NS2B-NS3 protease by mimicking arginine and binding tightly to the active site. These mimetic structures will be attached to different molecules via a free amine. The molecules will then be tested in competitive enzyme assays for the WNV NS2B-NS3 protease.