All ETDs from UAB

Advisory Committee Chair

Peter E Prevelige

Advisory Committee Members

William J Britt

Beatrice H Hahn

Ming Luo

Ruiwen Zhang

Document Type


Date of Award


Degree Name by School

Doctor of Philosophy (PhD) Heersink School of Medicine


The aim of this work was to build an understanding of the protein/protein interactions involved in HIV-1 capsid assembly as it relates to the condensation of capsid within the virion. This was undertaken in an attempt to (i) understand how capsid subunits recognize and interact with each other, (ii) gain insight into the protein-protein interactions involved in the process, and (iii) determine if the protein-protein interactions involved in virus cap-sid assembly can be used as a target for viral inhibition. Within this dissertation you will find two approaches to this investigation. The first examines the role of electrostatics in the in-vitro assembly of HIV-1 capsid through the use of select amino acid mutations. The second searches for small molecules that could inhibit or alter the protein/protein interactions involved in capsid assembly. This was accomplished by screening for restriction of an in-vitro capsid assembly assay as the initial consideration tool. Of the 10,000 compounds screen 114 compounds were shown to strongly disrupt capsid assembly in-vitro. Ninety-six of the strong inhibitors were screened in a series of cell-culture based assays with fully infectious virus for the ability to inhibit virus infectiv- ii ity or viral production. In addition, the degree of toxicity of the compounds to the cells was also monitored. The second selection tool yielded six potential compounds. At-tempts to elucidate the mechanism of action of these six compounds are described. Three of the six compounds are shown to primarily exert their anti-viral effect during the sec-ond half of the viral life-cycle.



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