Journal Article

SARS-CoV-2 tropism, entry, replication, and propagation: Considerations for drug discovery and development

Swaminathan, Gokul, Olsen, David B., Flynn, Jessica, Howell, Bonnie, Lieberman, Linda A., Klein, Daniel, Therien, Alex G., Murgolo, Nicholas, Adam, Gregory C., Hazuda, Daria J., Koeplinger, Kenneth, McKenna, Philip

2021

Overview

Since the initial report of the novel Coronavirus Disease 2019 (COVID-19) emanating from Wuhan, China, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has spread globally. While the effects of SARS-CoV-2 infection are not completely understood, there appears to be a wide spectrum of disease ranging from mild symptoms to severe respiratory distress, hospitalization, and mortality. There are no Food and Drug Administration (FDA)-approved treatments for COVID-19 aside from remdesivir; early efforts to identify efficacious therapeutics for COVID-19 have mainly focused on drug repurposing screens to identify compounds with antiviral activity against SARS-CoV-2 in cellular infection systems. These screens have yielded intriguing hits, but the use of nonhuman immortalized cell lines derived from non-pulmonary or gastrointestinal origins poses any number of questions in predicting the physiological and pathological relevance of these potential interventions. While our knowledge of this novel virus continues to evolve, our current understanding of the key molecular and cellular interactions involved in SARS-CoV-2 infection is discussed in order to provide a framework for developing the most appropriate in vitro toolbox to support current and future drug discovery efforts.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: ACE2 / Angiotensin / Angiotensin-converting enzyme 2 / Antiviral activity / Antiviral drugs / Autophagy / Biology / Biology and life sciences / C-reactive protein / Cathepsin L / Cathepsins / Cell Line / Cell lines / Conversion / Coronaviruses / COVID-19 / COVID-19 - virology / COVID-19 Drug Treatment / Drug Development / Drug Discovery / Endocytosis / Endoplasmic reticulum / Epithelial cells / Epithelium / Furin / Glucocorticoids / Humans / Mechanical ventilation / Medicine and health sciences / Middle East respiratory syndrome / Neuropilin / Nucleotides / Peptidyl-dipeptidase A / Phagocytosis / Propagation / Proteins / Respiratory diseases / Review / SARS-CoV-2 - drug effects / SARS-CoV-2 - physiology / Serine Endopeptidases / Severe acute respiratory syndrome / Severe acute respiratory syndrome coronavirus 2 / Subgroups / Tropism / Ventilation / Viral diseases / Viral Tropism / Virus Internalization / Virus Replication / Viruses