Conclusion
While previous screens used live coronaviruses or pseudoviruses, largely focused on viability for selection, here we have used SARS-CoV-2 spike and VSV-G enveloped pseudoviruses to focus a screen/counter screen strategy for viral entry (Baggen et al., 2021; Daniloski et al., 2021; Schneider et al., 2021; Wang et al., 2021; Wei et al., 2021). Our results indicate that delivery of CRE protein in the virion helped distinguish genes that play role in entry rather than retro-transcription from lentiviral reporters. Further development of this approach will be needed along to include CRE reporter in SARS-CoV-2 Spike pseudotyped cells. Thus, we view our screen is a proof of concept and that higher resolution data can be obtained by increasing the numbers of cells analyzed. Our screen identified novel genes that were not found in previously published screens suggesting that refining the selection strategy for screening should make it possible to identify mechanisms by which host genes facilitate and inhibit viral entry.