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).