First, viral proteins located on the virus' outer capsid bind to particular receptors on the host cell's surface. Next, virions enter the cell, either by fusing their membranes with those of the host cell or through the process of endocytosis, in which the host cell takes in the virion in a membrane-bound vesicle. The virion is now in a position to begin the replication cycle, releasing its genetic material into the cell. The viral genome encodes genes that when expressed, yield the protein components necessary to assemble new virus particles.
Hogue stresses the importance of in silico analysis, in which large libraries of proteins can be screened through analysis, in order to identify conserved and non-conserved protein regions, thus greatly accelerating the pace of discovery. "The more we learn about these particular regions of proteins that are critically important for the assembly process," she says, "the likelier it is we can design molecules that will be able to interfere with this process."
While some conserved domain alterations in the M protein proved lethal to coronaviruses, others undermined viral assembly without shutting it down completely, often causing compensatory efforts on the part of the virus, (known as second site changes) which may offer insights into the virus' adaptive capabilities. In the coming year, Hogue plans to examine the non-lethal changes introduced, studying these mutant viruses under high-resolution cryo-EM, to determine how alterations of specific domains affect overall coronaviral structure.
Additionally, Hogue's group is closely examining the under-represented envelope or E protein. "One reason we are excited about this is that a number of enveloped viruses, including hepatitis C, infl
|Contact: Joseph Caspermeyer|
Arizona State University