3.8 Any validation for functional connections with SARS-CoV-2?
We tested whether BCG-CGS, CMap positive connections, or predicted key hubs will have any impact on COVID-19 by identifying overlaps with SARS-CoV-2 interactome, i.e., human proteins that were experimentally validated to interact with SARS-CoV-2 and extracted from two recent reports. This analysis (Figure 4A) validated 3 proteins hits to have physical links to SARS-CoV-2. The three proteins are transcribed by: BRD4, PRKACA and SIRT5; they all were positive connections from the CMap, predicted as statistically significant key hubs, and were also validated SARS-CoV-2 interacting proteins.
Additionally, 14 high-confidence CMap positive connections, were validated to make physical interactions SARS-CoV-2 proteins. These proteins are: PSEN2, PABPC1, HMOX1, CIT, PLAT, IGF2R, RIPK1, NDUFS3, NDUFA5, GGH, NEU1, SCARB1, CSNK2B, F2RL1. And two positive connections, MARK2 and MARK3, were reported to have interactions with corona viruses. Predicted causal key hubs, SIGMAR1 and GNB1, were also validated to have physical links to SARS-CoV-2, and a third key hub PPIA was known as human protein interacting with proteins from corona viruses.
Additionally, we mined the biomedical literature to identify evidence for linking BCG small molecule mimics with SARS-CoV-2, corona viruses or viral infections in general. We found that two out of ten top positive compound connections (emetine and lopinavir), were recently validated to inhibit SARS-CoV-2 replication in vitro. Other compounds we found to inhibit the growth of corona viruses, or had general antiviral activities (Table 2).