Center for Antiviral Medicines & Pandemic Preparedness (CAMPP)

SUMMARY The ongoing COVID-19 pandemic has brought to light an urgent need to enhance the therapeutic preparedness for future viral outbreaks and pandemics. The overarching goal of the “Center for Antiviral Medicines & Pandemic Preparedness” (CAMPP) is thus to develop novel strategies and enhance the drug discovery pipelines for direct-acting antivirals against RNA viruses of pandemic concern. The specific focus of CAMPP will be to develop antivirals against coronaviruses SARS-CoV-2 (SCV2), SARS and MERS; flaviviruses including Zika, West Nile and Dengue virus; and hemorrhagic fever viruses including the filovirus Ebola, and bunyaviruses Severe fever with thrombocytopenia syndrome virus and Lassa virus. Infection by any of these agents has the potential to cause severe human disease with significant mortality rates and current options for antiviral treatments are limited. The antiviral drug remdesivir and several monoclonal antibody treatments have received emergency use authorization (EUA) for treatment of COVID-19, and the polymerase inhibitor molnupiravir by Merck is expected to be granted EUA in the near future. Monoclonal antibodies are also available to treat Ebola virus infection, however, none of these drugs can be administered orally, posing additional challenges in treating early infection. There are no approved treatments for the CAMPP flaviviruses and hemorrhagic fever viruses. Toward this end, we have assembled a world class multidisciplinary team of investigators with expertise in virology of relevant viruses, structural and computational biology, chemoproteomics, pharmacology and organoid/animal models, who will work closely with the drug development experts at the drug discovery division of The Scripps Research Institute, Calibr, to further the development of four major classes of promising assets in our drug discovery pipeline. First, we propose to develop a potentially best-in-class, orally bioavailable coronavirus protease (CLpro) inhibitor for coronaviruses including SCV2, from a late-stage drug asset undergoing ADME optimization that is expected to enter IND-enabling studies within the next three years. Second, we will identify and optimize RNA polymerase inhibitors for SCV2 and other CAMPP viruses, with the goal of reaching IND-enabling studies within the next four years. The third focus of our proposal is to develop antivirals against other ‘druggable’ proteins encoded by SCV2 and additional viruses posing a pandemic threat; these assets include inhibitors of SCV2 helicase, E-protein encoded ion channel activity, entry and fusion activities, and nucleocapsid, with the goal of obtaining in vivo proof-of-concept for a subset of these mid-stage assets. Finally, we propose to target traditionally considered ‘undruggable’ non-enzymatic proteins including SCV2 and flaviviral structural proteins as well as RNA structure, to develop novel strategies for antiviral drug development. CAMPP provides a highly integrated infrastructure of investigators, expertise and external pharmaceutical and founding partners that will ensure the Center’s success in achieving our goals and navigating challenges of the drug discovery process.