Presentation Title

Synthesis of Peptidomimetics for Inhibition of NS2B/NS3 Protease

Start Date

November 2016

End Date

November 2016

Location

HUB 302-5

Type of Presentation

Poster

Abstract

The West Nile virus (WNV) is commonly spread to humans by infected mosquitos and has spread globally to Africa, Europe, Asia, as well as North America. WNV is dependent on the feeding cycle of infected mosquito carriers, which allows the virus to remain a prevalent threat. Millions of people are infected every year with approximately 1% of WNV cases leading to a fatal neurological condition. Currently, there are no vaccines or other therapeutic methods to treat WNV infections, only mosquito control is a viable method of lowering WNV infections. The virus contains a (+)ssRNA and a viral envelope which allows for invasion of the host cell. Encapsulated RNA is used to translate a polypeptide to produce three structural and seven non-structural peptides. Successful replication in host cells depends on the modification of the viral polypeptide into active viral proteins, which are transported out of the cell by exocytosis. The viral NS2B-NS3 protease is part of the genomic polyprotein involved in WNV replication. The peptide complex contains a serine protease, nucleoside triphosphate, and helicase activity. Inhibiting the protease activity of NS2B-NS3 protein would affect WNV infection. A small molecule inhibitor could prevent the enzymatic activity, thereby ending WNV replication in host cells. Using organic synthesis, our research focuses on the development of mimetics for arginine and lysine that are known to bind strongly to the NS2B-NS3 Protease. These include arginine and lysine peptidomimetics and heterocyclic arginine mimetics. Potential inhibitors will be evaluated in competitive enzyme assays for WNV NS2B-NS3 protease inhibition.

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Nov 12th, 1:00 PM Nov 12th, 2:00 PM

Synthesis of Peptidomimetics for Inhibition of NS2B/NS3 Protease

HUB 302-5

The West Nile virus (WNV) is commonly spread to humans by infected mosquitos and has spread globally to Africa, Europe, Asia, as well as North America. WNV is dependent on the feeding cycle of infected mosquito carriers, which allows the virus to remain a prevalent threat. Millions of people are infected every year with approximately 1% of WNV cases leading to a fatal neurological condition. Currently, there are no vaccines or other therapeutic methods to treat WNV infections, only mosquito control is a viable method of lowering WNV infections. The virus contains a (+)ssRNA and a viral envelope which allows for invasion of the host cell. Encapsulated RNA is used to translate a polypeptide to produce three structural and seven non-structural peptides. Successful replication in host cells depends on the modification of the viral polypeptide into active viral proteins, which are transported out of the cell by exocytosis. The viral NS2B-NS3 protease is part of the genomic polyprotein involved in WNV replication. The peptide complex contains a serine protease, nucleoside triphosphate, and helicase activity. Inhibiting the protease activity of NS2B-NS3 protein would affect WNV infection. A small molecule inhibitor could prevent the enzymatic activity, thereby ending WNV replication in host cells. Using organic synthesis, our research focuses on the development of mimetics for arginine and lysine that are known to bind strongly to the NS2B-NS3 Protease. These include arginine and lysine peptidomimetics and heterocyclic arginine mimetics. Potential inhibitors will be evaluated in competitive enzyme assays for WNV NS2B-NS3 protease inhibition.