Abstract
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.
Highlights
Coronaviruses, named for their crown-like spiked surface, are genetically diverse and can infect multiple animal species, including bats, pigs, cats, rodents, and humans [1]
The most important decisions are the choice of cell line or model systems in which to conduct the screen and the availability of relevant secondary screens to eliminate irrelevant hits and prioritize those of potential interest
In this regard, assessing antiviral potency for SARS-CoV-2 viral replication should take into account the following key considerations
Summary
Coronaviruses, named for their crown-like spiked surface, are genetically diverse and can infect multiple animal species, including bats, pigs, cats, rodents, and humans [1]. Alpha and beta coronaviruses are known to infect humans, resulting in pathology ranging from upper respiratory. PLOS PATHOGENS symptoms typical of the common cold to life-threatening lower respiratory disease. From 2003 to mid-2019, 2 beta coronaviruses of zoonotic origin have caused outbreaks of severe respiratory disease: Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and Middle East Respiratory Syndrome Coronavirus (MERS-CoV). SARS-CoV emerged in Asia in February 2003 and spread to 26 countries before the outbreak was contained [3,4]. Over 8,000 people were infected with a case fatality rate of approximately 10% [5]. MERS-CoV first appeared in 2012 with early cases emanating from Saudi Arabia and Jordan. While human-to-human transmission for MERS-CoV is rare, the case fatality rate is greater than 30% [3,7]
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