Foundational research and NIH funding enabling Emergency Use Authorization of remdesivir for COVID-19

Abstract

ABSTRACTEmergency Use Authorization for remdesivir months after discovery of COVID-19 is unprecedented. Typically, decades of research and public-sector funding are required to establish the mature body of foundational research requisite for efficient, targeted drug discovery and development. This work quantifies the body of research related to remdesivir’s biological target, RNA-dependent RNA polymerase (RdRp), or parent chemical structure, nucleoside analogs (NcAn), through 2019, as well as NIH funding for this research 2000–2019. There were 6,567 RdRp-related publications in PubMed, including 1,263 with NIH support, and 11,073 NcAn-related publications, including 2,319 with NIH support. NIH support for RdRp research comprised 2,203 Project Years with Costs of $1,875 million. NIH support for NcAn research comprised 4,607 Project Years with Costs of $4,612 million. Research Project grants accounted for 63% and 48% of Project Years for RdRp and NcAn respectively, but only 19% and 12% of Project Costs. Analytical modeling of research maturation estimates that RdRp and NcAn research passed an established maturity threshold in 2008 and 1994 respectively. Of 97 investigational compounds targeting RdRp since 1989, the three authorized for use entered clinical trials after both thresholds. This work demonstrates the scale of foundational research on the biological target and parent chemical structure of remdesivir that supported its discovery and development for COVID-19. This work identifies $6.5 billion in NIH funding for research leading to remdesivir, underscoring the role of public sector investments in basic research and research infrastructure that underlie new drugs and the response to emergent disease.SIGNIFICANCE STATEMENTEmergency Use Authorization of remdesivir for treating COVID-19 four months after discovery of this virus was enabled by decades of research on the drug’s biological target as well as other medicines with related chemical structures. The NIH contributed 6,800 years of grant funding to this research, totaling $6.5 billion (2000–2019), including funding for both investigator-initiated research and research infrastructure. Of this, $46.5 million was for research directly related to remdesivir. This analysis demonstrates the importance of a robust body of foundational research in responding rapidly to emergent diseases, and the substantial NIH contribution to this research. It also underscores the scale and significance of the public-sector investments that enable new drug discovery and development.