Identification and Development of Therapeutics for COVID-19
Halie M. Rando,
Nils Wellhausen,
Soumita Ghosh,
Alexandra J. Lee,
Anna Ada Dattoli,
Fengling Hu,
James Brian Byrd,
Diane N. Rafizadeh,
Ronan Lordan,
Yanjun Qi,
Yuchen Sun,
Christian Brueffer,
Jeffrey M. Field,
Marouen Ben Guebila,
Nafisa M. Jadavji,
Ashwin N. Skelly,
Bharath Ramsundar,
Jinhui Wang,
Rishi Raj Goel,
YoSon Park,
Simina M. Boca,
Anthony Gitter,
Casey S. Greene
Affiliations
Halie M. Rando
Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania, USA
Nils Wellhausen
Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania, USA
Soumita Ghosh
Institute of Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
Alexandra J. Lee
Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania, USA
Anna Ada Dattoli
Department of Systems Pharmacology & Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
Fengling Hu
Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania, Philadelphia, Pennsylvania, USA
James Brian Byrd
University of Michigan School of Medicine, Ann Arbor, Michigan, USA
Diane N. Rafizadeh
Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
Ronan Lordan
Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
Yanjun Qi
Department of Computer Science, University of Virginia, Charlottesville, Virginia, USA
Yuchen Sun
Department of Computer Science, University of Virginia, Charlottesville, Virginia, USA
Christian Brueffer
Department of Clinical Sciences, Lund University, Lund, Sweden
Jeffrey M. Field
Department of Systems Pharmacology & Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
Marouen Ben Guebila
Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, USA
Nafisa M. Jadavji
Biomedical Science, Midwestern University, Glendale, Arizona, USA
Ashwin N. Skelly
Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
Bharath Ramsundar
The DeepChem Project
Jinhui Wang
Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
Rishi Raj Goel
Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
YoSon Park
Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania, USA
Simina M. Boca
Innovation Center for Biomedical Informatics, Georgetown University Medical Center, Washington, DC, USA
Anthony Gitter
Department of Biostatistics and Medical Informatics, University of Wisconsin—Madison, Madison, Wisconsin, USA
Casey S. Greene
Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, Colorado, USA
ABSTRACT After emerging in China in late 2019, the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread worldwide, and as of mid-2021, it remains a significant threat globally. Only a few coronaviruses are known to infect humans, and only two cause infections similar in severity to SARS-CoV-2: Severe acute respiratory syndrome-related coronavirus, a species closely related to SARS-CoV-2 that emerged in 2002, and Middle East respiratory syndrome-related coronavirus, which emerged in 2012. Unlike the current pandemic, previous epidemics were controlled rapidly through public health measures, but the body of research investigating severe acute respiratory syndrome and Middle East respiratory syndrome has proven valuable for identifying approaches to treating and preventing novel coronavirus disease 2019 (COVID-19). Building on this research, the medical and scientific communities have responded rapidly to the COVID-19 crisis and identified many candidate therapeutics. The approaches used to identify candidates fall into four main categories: adaptation of clinical approaches to diseases with related pathologies, adaptation based on virological properties, adaptation based on host response, and data-driven identification (ID) of candidates based on physical properties or on pharmacological compendia. To date, a small number of therapeutics have already been authorized by regulatory agencies such as the Food and Drug Administration (FDA), while most remain under investigation. The scale of the COVID-19 crisis offers a rare opportunity to collect data on the effects of candidate therapeutics. This information provides insight not only into the management of coronavirus diseases but also into the relative success of different approaches to identifying candidate therapeutics against an emerging disease. IMPORTANCE The COVID-19 pandemic is a rapidly evolving crisis. With the worldwide scientific community shifting focus onto the SARS-CoV-2 virus and COVID-19, a large number of possible pharmaceutical approaches for treatment and prevention have been proposed. What was known about each of these potential interventions evolved rapidly throughout 2020 and 2021. This fast-paced area of research provides important insight into how the ongoing pandemic can be managed and also demonstrates the power of interdisciplinary collaboration to rapidly understand a virus and match its characteristics with existing or novel pharmaceuticals. As illustrated by the continued threat of viral epidemics during the current millennium, a rapid and strategic response to emerging viral threats can save lives. In this review, we explore how different modes of identifying candidate therapeutics have borne out during COVID-19.