Hepatitis C Virus Non-structural Protein 3 (HCV NS3): A Multifunctional Antiviral Target

Kevin D. Raney, Suresh D. Sharma, Ibrahim M. Moustafa and Craig E. Cameron

Kevin D. Raney

Kevin D. Raney

Current position: Professor and chairman of the department of biochemistry and molecular biology at the University of Arkansas for Medical Sciences

Education: Ph.D. in organic chemistry in 1992 from Vanderbilt University

Nonscientific interests: Traveling with family, hiking, canoeing and spelunking

I became interested in how DNA is manipulated by enzymes while a graduate student in Tom Harris' lab at Vanderbilt University. I was studying the interaction between carcinogens and DNA, and I wondered how enzymes were able to handle bulky DNA adducts. This curiosity led me to join Steve Benkovic's lab to study nucleic acid enzymology. As a postdoc, I was able to pursue many different aspects of DNA replication and became fascinated with helicases -- in particular, their biochemical mechanisms. My interest in helicases overlapped with Craig Cameron's interest in RNA viral genome replication, so, soon after we each had our own labs, we began working together. In 1998, we began our collaboration focusing on the helicase from the hepatitis C virus, NS3, which is an RNA helicase that also functions well on DNA. There have been numerous breakthroughs and surprises over the years in the field of helicase enzymology, but there are far more questions remaining to be answered.

Read Raney's article on page 22725.

Suresh D. Sharma

Suresh D. Sharma

Current position: Research associate at the department of biochemistry and molecular biology at The Pennsylvania State University

Education: Ph.D. in life sciences in 1999 from the University of Mumbai

Nonscientific interests: Reading, digital photography, yoga and listening to music

Incidents of viral infections make the headlines almost every week. I became interested in virology after learning about how viruses hijack the host cellular machinery to duplicate their genetic material. Subsequently, my interest in the study of positive-strand RNA viruses deepened while I was a CSIR-research associate at the Cancer Research Institute. These viruses cause a multitude of diseases. Examples of positive-strand RNA viruses include poliovirus, coxsackie virus, echovirus, yellow fever virus, a relative of dengue and West Nile virus in the same family as Hepatitis C Virus (HCV).

I became interested in studying HCV, a virus that causes persistent infection and often leads to cirrhosis and hepatocellular carcinoma. At present, there is neither a selective antiviral therapy nor a preventive vaccine. The only available treatment option is pegylated-interferon-alpha, which, given in combination with the nucleoside analog ribavirin, is not very effective. A complete understanding of the functional roles played by HCV proteins during the HCV lifecycle is crucial for developing a successful cure.

My interest in discovering novel targets with therapeutic potential led me to the laboratory of Craig Cameron at The Pennsylvania State University. I am currently investigating the processes of HCV RNA replication at the level of cell biology. In collaboration with Kevin Raney, we were able to identify residues on the surface of NS3 helicase that are required for optimal replication of the Hepatitis C Virus.

Read Sharma's article on page 22725.

Ibrahim M. Moustafa

Current position: Research associate at the department of biochemistry and molecular biology at The Pennsylvania State University

Education: Ph.D. in chemistry (structural biology) in 2004 from the University of St. Andrews in the United Kingdom

Nonscientific interests: Reading, watching movies and traveling

One thing that fascinated me as a chemistry student was the relationship between the structure and function of molecules. As a graduate student, I became interested in studying protein structures using X-ray crystallography and molecular modeling techniques. During my postdoctoral training, my interest in exploring the structures of these magnificent molecules continued to increase and extended to go beyond the static view obtained from crystallography.

Currently, I apply the combination of X-ray crystallography and molecular dynamics simulation to get deep insights into how enzymes work. In Craig's laboratory I had the chance to work on HCV NS3 protein, which is very attractive to study, as it is an important target for drug development against HCV.

Read Moustafai's article on page 22725.

Craig E. Cameron

Craig E. Cameron

Current position: Paul Berg professor at the department of biochemistry and molecular biology at The Pennsylvania State University

Education: Ph.D. in biochemistry in 1993 from Case Western Reserve University

Nonscientific interests: Traveling, cooking (and eating), singing, dancing and fitness

I was in college when HIV (known then as HTLV-III) was discovered and became completely enthralled by virus biology, host responses to infection, antivirals and vaccines. I did my graduate work with Jonathan Leis in the biochemistry department at Case Western Reserve University, where I studied retroviral proteases, including HIV protease. This work highlighted the importance of being able to combine structure with studies of enzyme mechanism to understand enzyme function. As a result, I complete postdoctoral studies with Steve Benkovic in the chemistry department at Penn State University. In my own research program, I apply a variety of approaches to answer fundamental questions about virus biology that contribute new platforms for antiviral and vaccine development.

Read Cameron's article on page 22725.