Non-canonical alternate interactors of SARS CoV-2 Spike protein implicated in placental susceptibilty
Vertical transmission of SARS-CoV-2 is controversial. Owing to the low expression of ACE2 along with TMPRSS2 in placenta, role of secondary receptors becomes significant. In our study we predicted twelve interactors of spike protein expressed in placenta through interactome analysis followed by docking and molecular dynamic simulation. Three interactors of SARS-CoV-2 spike protein were found to…
A recent study has identified three alternate interactors of the SARS-CoV-2 Spike protein that may play a role in placental susceptibility to the virus. The researchers used interactome analysis and docking simulations to predict twelve potential interacting proteins expressed in placenta. Further experiments confirmed that CD147, EGFR, and LDLR were expressed in placenta samples from women with COVID exposure risk.
Using PCR and immunohistochemistry, the researchers found elevated protein levels of CD147, ACE2, and LDLR in those with higher exposure risk. However, the variation in mRNA expression was not statistically significant. Computational studies revealed that CD147/basigin, EGFR, and LDLR could interact with the Spike protein outside its primary receptor binding domain.
In-vitro binding assays supported this finding, and in-silico site-directed mutagenesis identified key binding hotspots on each receptor. The study concludes that these three proteins may function as secondary non-canonical cofactors for the Spike protein in placenta, potentially increasing its susceptibility and tissue tropism.
The findings provide valuable insights into placental susceptibility, offering targeted therapeutic opportunities.
Written by urgent.news from bioRxiv's reporting — not their text. Machine-written — may contain errors; check the original before relying on it.
