Our lab is interested on the roles that cellular proteins and lipids play in infection, replication and pathogenesis of viruses and prions, with the ultimate goal of finding novel antiviral drugs. As a model for our studies, we use viruses such as herpes simplex or hepatitis C virus (HSV or HCV, respectively), and prions such as scrapie.

We use chemical biology with novel (experimental) drugs to identify cellular functions required for viral infection, replication, or pathogenesis. Using such approaches, we have discovered that cellular cyclin-dependent kinases (CDKs) are required to activate transcription form the extra-chromosomal HSV genomes. CDKs regulate progression into the different phases of the cell-cycle. Our results suggest that they may also be involved in innate cellular defense mechanisms against viral infections. We are currently analyzing these mechanisms, which may involve chromatin silencing, using standard and state-of-the-art virology, biochemistry, and molecular and cell biology techniques.

CDKs are only rarely expressed in non-cycling neurons. We have shown, however, that neuronal expression of CDKs is induced by the same stimuli that promote neuronal HSV replication. Neuronal deregulation of cellular protein kinases is thought implicated in several neurological diseases, such as Alzheimer's or Parkinson’s. We postulate that deregulation of certain cellular protein kinases is also important in neuropathogenesis of infectious diseases. We are particularly interested in the transmissible spongiform encephalopathies (TSE), or prion disease. TSEs are atypical infectious diseases, invariably fatal, that affect domestic and wild ruminants and human beings. There is no treatment or vaccine against TSEs, and their pathogenic mechanisms are still poorly understood. We are analyzing the roles of cellular protein kinases in TSE pathogenesis, using novel kinomic approaches developed in our group. We aim at identifying the protein kinases that play crucial roles in such pathogenesis, with the ultimate goal of using them as targets for novel treatments against TSEs.

Viral infection starts with entry of extracellular virions into cells, a function that is considered a desirable target for antiviral drugs. However, all entry inhibitors target the viral proteins involved in this process and consequently suffer of certain limitations. We have identified a novel family of viral entry inhibitors with unique mechanisms of action and targets, which do not suffer of similar limitations. We are now further characterizing these drugs, their mechanisms of action, and their potential to be developed as novel antivirals.

We are currently interested in four major areas of research: 1) the mechanisms whereby cellular protein kinases regulate the activation of transcription of viral genes; 2) the roles of cellular protein kinases in prion diseases; 3) the potential of inhibitors of cellular proteins required for replication or pathogenesis of infectious agents as anti-infective drugs; and 4) the full characterization of the potential of our novel compounds as antiviral drugs.