Physics professors pioneer method to study untreatable strains of hepatitis C virus
Physics professors Mohammad Yousef and Edward Ackad
Physics professors Mohammad Yousef and Edward Ackad developed a method to predict the behavior of the Egyptian strain of hepatitis C virus, which has no known cure.
By studying the American genotype, they built a 3-D structural model that could lead to advances in medicine and, ultimately, a cure. Their method prompted scientists around the world to approach them about their research in hopes of learning to treat strains of hepatitis C within their own countries.
According to Yousef, their analysis of the hepatitis strain, which affects 20 percent of Egypt’s population, has findings that are “landmark and universally applicable.”
“Within two months of our article’s publication online by the ‘Journal of Biomolecular Structure and Dynamics’ it became one of the website’s most-read articles, ranking fourth among downloads,” Yousef said.
To model the behavior of the virus posed a challenge, according to Yousef. They needed to study the proteins that are essential to the life cycle of the virus, but the proteins are too small to be observed through a conventional microscope. However, through an experimental technique called crystallography, where x-ray light is shone on the protein crystals, with sufficient resolution, it was possible to capture a 3-D image of the proteins.
The 3-D picture Yousef used to build a model prediction of the Egyptian strain based on the crystal structure of the American one.
The building blocks of proteins are amino acids which one can imagine as beads, according to Yousef. With each bead thread folded into a 3-D structure after being threaded to the American version, they then used software to analyze the threaded version of the Egyptian strain.
They used this 3-D image to predict the behavior of the Egyptian strain using computational tools, such as molecular dynamics simulation – a technique by which each atom of the protein is moved according to its bonds and local environment.
Their final model didn’t clash with itself when threaded on the American virus strain, which confirms the validity of their model, according to Yousef.
Yousef said the process of molecular dynamics simulation had never been used on the Egyptian strain.
“We used tools that are available to scientists all over the world,” Yousef said. “We just innovatively applied it to study the Egyptian strain.”
Ackad said there are hydrogen bonds between three important amino acids of both the American and Egyptian strains. These three amino acids are the active part of the protein that does the work.
“However, in the Egyptian strain, the bonds are much looser which implies that they are significantly weaker,” Ackad said. “This reveals something in the behavior of how the strain works and may be the basis for the drug resistance of this strain.”
Yousef said the Egyptian virus evolved so that it is somewhat weaker, but at the same time it became “bullet proof” and evades drugs. By understanding the “bullet” proof mechanism we can design better “bullets”.
“It’s opening more questions related to drug resistivity seen and we think that this method could be universally applicable to other viruses as well,” Yousef said.
In their proposed next phase of research, Yousef and Ackad will examine how both genotypes interact with drugs. For example, they will try to determine how the difference in movements translates into drug resistance.
They now have both a 3-D static look to and a video of the behavior of an essential piece of the virus. A movie they produced displays the behavioral differences between the Egyptian and American versions of the virus.
Their collaborator in Egypt, Professor Salwa Sabet, of Cairo University Department of Zoology, analyzed the sequence of the amino acids. SIUE funded the project’s open access journal publication while the Wellcome Trust-Burroughs Infectious Diseases Initiative provided partial funds.
Department chair Abdullatif Hamad said the physics department is proud of the research collaboration between Ackad and Yousef.
“The first result of this collaboration is this high quality paper that was viewed by over 300 researchers within the first month of its publication,” Hamad said.
Filed Under: General CAS Stories • Physics
