Vishwanath Rao Lingappa, MD, PhD
As of 2005 my laboratory has moved from UCSF and my research interests have refocused on novel antiviral drug development at Prosetta Antiviral, Inc, the biotechnology firm I have founded and for which I serve as Chief Technology Officer and CoCEO. Prosetta has licensed the cell-free capsid protein synthesis and assembly system we pioneered in the 1990's at the UCSF academic laboratory. That platform was adapted to small molecule screening and has allowed us to identify a plethora of small molecules robustly active against each of the major commercial and public health relevant viruses, irrespective of strain. We have proof of concept evidence for efficacy in animals (100% protection of mice against 1000 LD50 mouse-adapted Ebola virus with four days of once daily therapy of one of our drugs, with protection observed even when drug was administered 24hrs after inoculation with the virus). We have demonstrated a barrier to resistance development, in the case of influenza virus, in cell culture. We have demonstrated that the targets are host proteins essential for the virus in ways that are not essential for the host and that the lead series displays a robust structure-activity relation with improvement in therapeutic index to > 100 for molecules active against HIV, Hepatitis C virus, Influenza, and a variety of other viruses of public health importance including rabies, chikungunya, and dengue virus. We have demonstrated two drug-induced phenotypes (blockade of virus release and release of non-infectious virus with aberrant capsids) that are as expected for targets in the host-catalyzed capsid assembly pathway. We now seek pharma or other partners to advance these molecules to IND filing and human clinical trials.