The branded pharmaceutical industry is a slow innovation industry, because of the long time to market of new molecular entities (NME). On average, it takes ~10-15 years from concept to product, at a cost of ~$1-5 billion, and a failure rate of ~90% [1]. There are generally two reasons why the timelines are long. One involves the linear phase sequencing of clinical trials and the other, is around financial risks around probability of technical and regulatory success. A perhaps more proximal issue is that pharmaceutical R&D enterprises are organized around prioritized investments, working on assets with the greatest return of investments. There is much less appreciation or flexibility in leveraging expertise around priorities that are often thrust on the system by external forces, such as the current pandemic. Addressing emerging public health concerns, including preparedness for epidemic/pandemic situations, requires a hypervelocity mindset, which the current apparatus is least prepared for. This commentary offers insight into the organizational preparedness into mobilizing resources and scientific creativity for accelerated timelines in response to pandemics.

Aim: We hypothesize that the efficacy of COVID-19 therapeutic candidates will be better predicted by understanding their effects at various points on a viral cell cycle, in particular, the specific rate constants, and that drugs acting independently of these specific discrete sites may not yield expected efficacy. We hypothesize that drugs, or combinations of drugs that act at specific multiple sites on the viral life cycle have the highest probability of success in the treatment of early infection phase in COVID-19 patients. Methods: Using a target cell limited model structure that had been used to characterize viral load dynamics from COVID-19 patients, we performed simulations to show that combinations of therapeutics targeting specific rate constants have greater probability of efficacy and supportive rationale for clinical trial evaluation. Results: Based on the known kinetics of the SARS-CoV-2 life cycle, we rank ordered potential targeted approaches involving repurposed, low-potency agents. We suggest that targeting multiple points central to viral replication within infected host cells or release from those cells is a viable strategy for reducing both viral load and host cell infection. In addition, we observed that the time-window opportunity for a therapeutic intervention to effect duration of viral shedding exceeds the effect on sparing epithelial cells from infection or impact on viral load AUC. Furthermore, the impact on reduction on duration of shedding may extend further in patients who exhibit a prolonged shedder phenotype. Conclusions: Our work highlights the use of model-informed tools to better rationalize effective treatments for COVID-19.