Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2020 Nov 11;28(5):638-645.
doi: 10.1016/j.chom.2020.09.017. Epub 2020 Oct 1.

Accelerated Preclinical Paths to Support Rapid Development of COVID-19 Therapeutics

Jay A Grobler  1 , Annaliesa S Anderson  2 , Prabhavathi Fernandes  3 , Michael S Diamond  4 , Christine M Colvis  5 , Joseph P Menetski  6 , Rosa M Alvarez  7 , John A T Young  8 , Kara L Carter  9
Affiliations
Review

Accelerated Preclinical Paths to Support Rapid Development of COVID-19 Therapeutics

Jay A Grobler et al. Cell Host Microbe. .

Abstract

When SARS-CoV-2 emerged at the end of 2019, no approved therapeutics or vaccines were available. An urgent need for countermeasures during this crisis challenges the current paradigm of traditional drug discovery and development, which usually takes years from start to finish. Approaches that accelerate this process need to be considered. Here we propose the minimum data package required to move a compound into clinical development safely. We further define the additional data that should be collected in parallel without impacting the rapid path to clinical development. Accelerated paths for antivirals, immunomodulators, anticoagulants, and other agents have been developed and can serve as "roadmaps" to support prioritization of compounds for clinical testing. These accelerated paths are fueled by a skewed risk-benefit ratio and are necessary to advance therapeutic agents into human trials rapidly and safely for COVID-19. Such paths are adaptable to other potential future pandemics.

PubMed Disclaimer

Conflict of interest statement

Declaration of interests Authors of the manuscript are members of ACTIV Preclinical Working group. Jay A Grobler is a shareholder in Merck. Annaliesa S Anderson is an employee of Pfizer, receives a salary from Pfizer and may own Pfizer stock; she is also a non-salaried member of the Contrafect Scientific Advisory Board. Michael S. Diamond is a consultant for Inbios, Vir Biotechnology, and NGM Biopharmaceuticals and is on the Scientific Advisory Board of Moderna and Immunome. The Diamond laboratory has received unrelated funding support in sponsored research agreements from Moderna, Vir Biotechnology, and Emergent BioSolutions. John A.T. Young is an employee and shareholder of F.Hoffmann-La Roche, Ltd. Kara Carter is on the Scientific Advisory Board for the Alabama Drug Discovery and Development Consortium and owns stock in Evotec and Celldex Therapeutics.

Figures

Figure 1
Figure 1
Comparison of the Processes for Traditional Drug discovery and Pandemic Response Mode
Figure 2
Figure 2
COVID-19: Stages, Symptoms, and Potential Treatments
Figure 3
Figure 3
Blueprints for Pandemic Response Mode for Antivirals and Immunomodulators for COVID-19
See this image and copyright information in PMC

References

    1. Alsuliman T., Alasadi L., Alkharat B., Srour M., Alrstom A. A review of potential treatments to date in COVID-19 patients according to the stage of the disease. Curr. Res. Transl. Med. 2020;68:93–104. - PMC - PubMed
    1. Arshad Ali S., Baloch M., Ahmed N., Arshad Ali A., Iqbal A. The outbreak of Coronavirus Disease 2019 (COVID-19)-An emerging global health threat. J. Infect. Public Health. 2020;13:644–646. - PMC - PubMed
    1. Bose S., Adapa S., Aeddula N.R., Roy S., Nandikanti D., Vupadhyayula P.M., Naramala S., Gayam V., Muppidi V., Konala V.M. Medical Management of COVID-19: Evidence and Experience. J. Clin. Med. Res. 2020;12:329–343. - PMC - PubMed
    1. Bouhaddou M., Memon D., Meyer B., White K.M., Rezelj V.V., Correa Marrero M., Polacco B.J., Melnyk J.E., Ulferts S., Kaake R.M. The Global Phosphorylation Landscape of SARS-CoV-2 Infection. Cell. 2020;182:685–712.e19. - PMC - PubMed
    1. Buonaguro F.M., Puzanov I., Ascierto P.A. Anti-IL6R role in treatment of COVID-19-related ARDS. J. Transl. Med. 2020;18:165. - PMC - PubMed