Access Type

Open Access Thesis

Date of Award

January 2017

Degree Type

Thesis

Degree Name

M.S.

Department

Biochemistry and Molecular Biology

First Advisor

Ladislau Kovari, PhD

Second Advisor

Robert Akins, PhD

Abstract

Abstract HIV-1:

Human immunodeficiency virus-1 (HIV-1) is a widespread, incurable retrovirus known to cause

immunodeficiency and a shortened life span. Despite successful treatment methods, HIV-1

frequently mutates, resulting in antiviral resistance. Many therapies target the HIV-1 protease

(PR), which is responsible for cleaving the viral polyprotein essential for its life cycle. HIV-1 PR

often evades treatment by way of mutations and less commonly through residue insertions. We

have identified a clinical isolate with a five residue insertion between residues 28 and 29.

Through molecular dynamics simulations we analyzed the protease protein structure and

determined that the residue insertion created a change in the secondary structure of the hinge

region of the viral protease. Elucidating the role of insertions could both aid in understanding

viral mutations as well as the theoretical effect on patient treatment/outcome.

Abstract Chikungunya:

Chikungunya virus (CHIKV) is an incurable Arbovirus creating the most notable symptom of

severe and sometimes chronic arthralgia. CHIKV is considered a neglected tropical virus by the

World Health Association (WHO), with the potential of becoming a larger scale threat in part

due to the influence of global warming on the mosquito population that serve as vectors for

CHIKV. The virus has a life cycle is dependent on its nonstructural protein function, one of

specific interest is nsP2. We have successfully expressed, optimized, and purified active CHIKV

nsP2. Future studies will look at small peptidomimetic drug design.

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