Drug Combinations as a First Line of Defense against Coronaviruses and Other Emerging Viruses
Judith M. White, Joshua T. Schiffer, Rachel Bender Ignacio, Shuang Xu, Denis E. Kainov, Aleksandr Ianevski, Tero Aittokallio, Matthew B. Frieman, Gene G. Olinger, Stephen J. Polyak
Abstract
and in the clinic, many studies employed solo drugs and had disappointing results. Here, we review drug combination studies against SARS-CoV-2 and other viruses and introduce a model-driven approach to assess drug pairs with the highest likelihood of clinical efficacy. Where component agents lack sufficient potency, we advocate for synergistic combinations to achieve therapeutic levels. We also discuss issues that stymied therapeutic progress against COVID-19, including testing of agents with low likelihood of efficacy late in clinical disease and lack of focus on developing virologic surrogate endpoints. There is a need to expedite efficient clinical trials testing drug combinations that could be taken at home by recently infected individuals and exposed contacts as early as possible during the next pandemic, whether caused by a coronavirus or another viral pathogen. The approach herein represents a proactive plan for global viral pandemic preparedness.