Open Access Thesis
Date of Award
Biochemistry and Molecular Biology
Ladislau Kovari, PhD
Robert Akins, PhD
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.
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.
Slater, Kristin Nicole, "Elucidating Structure, Function, And Small Molecular Interactions Of Human Immunodeficiency Virus And Chikungunya Virus" (2017). Wayne State University Theses. 587.