Thread by @outbreakupdates

SARS-CoV-2 Hijacks Cellular Command 🧵

YAP is a crucial switchboard operator in a communication network, the Hippo pathway.

It’s responsible for managing vital signals that regulate cell growth and immune responses.

1/

NSP13 of SARS-CoV-2 is a crucial component of the virus’s replication and transcription complex.

NSP13 doesn’t just cut the wires to this switchboard (as direct inhibition would).

Instead, it slips into the switchboard room unnoticed and starts rerouting calls.

2/

NSP13 binds with TEAD4, a critical collaborator of YAP in this communication network.

This binding is like NSP13 bringing in its own team (CCT3 and TTF2) to take over the switchboard.

These new operators don’t shut down the system; they change the connections.

3/

The signals that should be going out are now either blocked or misdirected.

YAP is still there, seemingly in control, but its instructions are now being manipulated.

NSP13’s helicase activity is the key to this operation.

4/

It’s like having a master key to access and rewire the communication lines.

It’s allowing NSP13 to effectively take over the YAP’s control panel without directly confronting it.

This hijacking leads to a malfunction in the Hippo pathway’s usual operation.

5/

It contributes to the tissue damage and immune dysfunction observed in severe COVID-19 cases.

6/6 biorxiv.org/content/10.110…