Coronaviruses (CoVs) are a group of positive-sense RNA viruses. These pathogens have caused several outbreaks in recent years, such as the severe acute respiratory syndrome (SARS) outbreak in 2003, Middle-East respiratory syndrome (MERS) outbreak in 2017, and the coronavirus disease (COVID-19) outbreak in 2019. Many strains of CoVs require BSL-3 facilities for live virus work. To facilitate in vitro studies on these viruses in a BSL-2 setting, Dr. Gary Whittaker’s lab at Cornell has developed a system for CoV pseudotyping using a murine leukemia virus (MLV) system to model CoV spike-mediated viral entry (Millet JK, et al. J Vis Exp. 2019 Mar 1;(145)). NCATS has collaborated with Dr Whittaker’s group to utilize this assay system for screening of small molecule compound libraries for inhibitors of SARS-S pseudotyped particle cell entry. To eliminate false positive compounds, ATP content cytotoxicity assay was screened in the same cell line.
Cherry picked hits from the primary screen were counter screened against additional VSV-G PP entry assay to further eliminate false positive compounds. Further details can be found in preprint: