Metropolitan AntiViral Drug Accelerator - ABSTRACT The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in millions of deaths worldwide. Novel vaccines against SARS-CoV-2 have altered the pandemic’s trajectory. Yet, large populations remain at risk, and immune escape virus variants threaten to thwart vaccine action or current therapies. New small molecule antiviral drugs available as oral treatments in the outpatient setting are needed to treat SARS-CoV-2 infections, other coronaviruses, and additional viruses of pandemic concern. COVID-19 has helped rejoin large Pharma in anti-infective drug development but there remains a gap in the early drug discovery phase, which can be met by academic scientists engaged in drug discovery through successful partnership with industry. Academic groups have great biological insights and platforms for novel discovery resulting in identification of new targets, Hits, and Leads. Yet, they rarely have the ways or means to optimize compounds and advance them for clinical development. We hypothesize that an effective public-private partnership can bridge this gap and have created the Metropolitan AntiViral Drug Accelerator (MAVDA). It is an unprecedented collaborative enterprise of academic and Pharma partners in New York City and Northern New Jersey brought together in a common discovery ecosystem to address the urgent need for validated small-molecule antiviral drugs. MAVDA combines world-class virologists and academic drug discovery researchers from Rockefeller University, Columbia University and Memorial Sloan- Kettering Cancer Center in New York City and the Center for Discovery and Innovation and Rutgers University in New Jersey with proven antiviral drug developers at Merck & Co., Inc., the Tri-Institutional Therapeutics Discovery Institute (Tri-I TDI)-Takeda Pharmaceuticals, and Aligos Therapeutics, as a cohesive enterprise to deliver new antiviral drugs. A critical innovation of the Accelerator is the establishment of an extensive and integrated network of Pharma-style science cores with highly experienced Core directors, which ensures that compound identification and optimization proceeds efficiently. Standardized threshold “gating” metrics for compound progression with clear ‘Go/No Go’ criteria will be established to support development of qualified drug candidates. MAVDA Projects unite academic and industry investigators with innovative and well-established drug discovery platforms with a strong emphasis on validated targets like 3CLpro, but also exploit other important targets like Nsp14 and Nsp16 MTase, ExoN, PLpro, Nsp13 helicase, RdRp, as well as novel targets. Promising Hits, early Leads, and Optimized Leads at or near the IND enabling/de-risking stage are represented, along with innovative approaches for new natural product discovery. All programs target SARS-CoV-2 but also address other coronaviruses, flaviviruses and/or alphaviruses. MAVDA is robust, easily accommodates Developmental projects and new virus challenges, and it is an ideal environment for training the next generation of scientists for drug discovery and pandemic preparedness.
