Abstract Title

HIV-1 protein interactions: protein-protein interaction sites as candidate drug targets

Abstract

The existing anti-retroviral therapies use combination of several inhibitory drugs targeting five different viral proteins at different steps in the viral life cycle as the virus infects target immune cells. However, rapid emergence of the drug-resistant HIV-1 mutants and serious adverse effects necessitate the need for further discovery of the new drugs and potential targets. Numerous studies have shown that protein-protein interactions play important roles in the viral life cycle and that inhibiting these interactions has a significant therapeutic potential. Yet, identifying the most promising targets, including specific protein regions directly involved in protein-protein interactions remains a challenge. Our recent bioinformatics study (Hetti Arachchilage and Piontkivska 2016) identified a set of interacting regions from integrase and reverse transcriptase. However, in order to expand the set of candidate interacting regions to other proteins involved in a multi-protein integration complex, we need to have a better understanding of molecular mechanisms of action (and interactions) throughout the HIV-1 life cycle. Thus, the purpose of this literature review-based study is to conduct a comprehensive survey of available biochemical studies that examine viral-viral protein interactions in HIV to identify potential protein domains and/or residues responsible for specific interaction outcomes. These domains/residues can be used in the future bioinformatics analyses to further elucidate their usability as promising drug targets.

Modified Abstract

The rapid emergence of the drug-resistant HIV-1 mutants demands further discovery of new drugs targets. Inhibiting protein-protein interactions that play important roles in the viral life cycle has a significant therapeutic potential. Yet, identifying most promising targets remains a challenge. Our recent bioinformatics study (Hetti Arachchilage and Piontkivska 2016) identified a set of interacting regions from integrase and reverse transcriptase. Future bioinformatics analyses to expand the set of candidate interacting regions to other viral proteins needs a better understanding of their molecular mechanisms of interactions. Thus, the purpose of this literature review-based study is to conduct a comprehensive survey of available biochemical studies that examine viral-viral protein interactions in HIV to identify potential protein domains/residues which can be further elucidated through future bioinformatics analyses.

Research Category

Biomedical Sciences

Author Information

Brett M. LowdenFollow

Mentor #1 Information

Madara Hetti Arachchilage

Mentor #2 Information

Dr. Helen Piontkivska

Presentation Format

Poster

Start Date

March 2016

Research Area

Epidemiology

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Mar 15th, 1:00 PM

HIV-1 protein interactions: protein-protein interaction sites as candidate drug targets

The existing anti-retroviral therapies use combination of several inhibitory drugs targeting five different viral proteins at different steps in the viral life cycle as the virus infects target immune cells. However, rapid emergence of the drug-resistant HIV-1 mutants and serious adverse effects necessitate the need for further discovery of the new drugs and potential targets. Numerous studies have shown that protein-protein interactions play important roles in the viral life cycle and that inhibiting these interactions has a significant therapeutic potential. Yet, identifying the most promising targets, including specific protein regions directly involved in protein-protein interactions remains a challenge. Our recent bioinformatics study (Hetti Arachchilage and Piontkivska 2016) identified a set of interacting regions from integrase and reverse transcriptase. However, in order to expand the set of candidate interacting regions to other proteins involved in a multi-protein integration complex, we need to have a better understanding of molecular mechanisms of action (and interactions) throughout the HIV-1 life cycle. Thus, the purpose of this literature review-based study is to conduct a comprehensive survey of available biochemical studies that examine viral-viral protein interactions in HIV to identify potential protein domains and/or residues responsible for specific interaction outcomes. These domains/residues can be used in the future bioinformatics analyses to further elucidate their usability as promising drug targets.