Identification of putative genes that natively inhibit SARS-CoV2 and VSVG entry.
We identified salt inducible kinase 2 and 3 (SIK2 and SIK3) as top negative regulators of Spike-mNG entry (Figure 3A). These serine/threonine protein kinases belonging to the AMPK protein family, and they have been shown to regulate glucose metabolism, mTORC signaling and hormonal signaling (Bricambert et al., 2010; Csukasi et al., 2018; Yang et al., 2013; Zhang et al., 2016). However, the mechanism by which these kinases might inhibit spike-mediated entry is unclear and we have not validated this finding. Additionally, GALNT11 was identified as a suppressing VSVG-mNG and VSVG-CRE entry and ALG5 in suppressing VSVG-CRE (Figure 3B and 3C). GALNT11 is an N-Acetylgalactosaminyltransferase and is involved in O-linked glycosylation of proteins in the Golgi, whereases ALG5 is involved in N-linked glycosylation of proteins (Imbach et al., 1999; Schwientek et al., 2002).