Date of Award


Degree Type


Degree Name

Doctor of Philosophy (PhD)


Mathematics and Natural Sciences

Committee Chair

Dr. Jacques J. Kessl

Committee Chair School

Mathematics and Natural Sciences

Committee Member 2

Dr. Fengwei Bai

Committee Member 2 School

Biological, Environmental, and Earth Sciences

Committee Member 3

Dr. Matthew G. Donahue

Committee Member 3 School

Mathematics and Natural Sciences

Committee Member 4

Dr. Faqing Huang

Committee Member 4 School

Mathematics and Natural Sciences

Committee Member 5

Dr. Julie A. Pigza

Committee Member 5 School

Mathematics and Natural Sciences


The human immunodeficiency virus type 1 (HIV-1) infection remains a global health crisis, necessitating the development of innovative antiviral strategies. During the integration step, HIV-1 integrase (IN) interacts with viral DNA and the cellular cofactor LEDGF/p75 to effectively integrate the reverse transcript into the host chromatin. Recently, a novel class of antiretroviral agents called Allosteric Inhibitors of HIV-1 Integrase (ALLINI) compounds has emerged as a promising avenue in the fight against HIV-1. While originally designed to inhibit IN-LEDGF/p75 interactions, these compounds have been shown to also impact late-stage viral maturation severely through IN multimerization. Induction of IN multimerization interferes with virion maturation through misvocalization of vRNA rendering them noninfectious. ALLINI compounds have shown potent antiviral activity against a broad range of HIV-1 strains, including drug-resistant variants. This abstract provides an overview of the use of the ALLINI compounds based on quinoline scaffold derivatives which have been shown to exhibit enhanced potency, prolonged antiviral activity, and reduced likelihood of resistance. Additionally, this research explores the inclusion of covalent warheads with the aim to optimize these compounds and explore their applications as a part of therapeutic strategies for HIV-1, offering new avenues for effective treatment strategies and their integration into future combination antiretroviral therapies.



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