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.