Thread by @ejustin46

𝗦𝗔𝗥𝗦-𝗖𝗼𝗩-2 𝗮𝗯𝗲𝗿𝗿𝗮𝗻𝘁𝗹𝘆 𝗲𝗹𝗲𝘃𝗮𝘁𝗲𝘀 𝗺𝗶𝘁𝗼𝗰𝗵𝗼𝗻𝗱𝗿𝗶𝗮𝗹 𝗯𝗶𝗼𝗲𝗻𝗲𝗿𝗴𝗲𝘁𝗶𝗰𝘀 𝘁𝗼 𝗶𝗻𝗱𝘂𝗰𝗲 𝗿𝗼𝗯𝘂𝘀𝘁 𝘃𝗶𝗿𝘂𝘀 𝗽𝗿𝗼𝗽𝗮𝗴𝗮𝘁𝗶𝗼𝗻 🔥

nature.com/articles/s4139…

2) SARS-CoV-2 infection aberrantly elevates mitochondrial bioenergetics and induces mitochondrial elongation during the early stages of infection in human cells. This promotes ATP generation to support robust viral replication.

3) SARS-CoV-2 increases mitochondrial membrane potential through the interaction of viral RNA and nucleocapsid protein. This leads to elongated mitochondria morphology.

4) Infection also enhances oxidative phosphorylation and expression of mitochondrial respiratory chain complexes to increase ATP production.
SARS-CoV-2 activates the EGFR signaling pathway and induces mitochondrial translocation of EGFR.

5) This contributes to sustaining the abnormal elevation in mitochondrial bioenergetics.
Treatment with FDA-approved EGFR inhibitors, especially vandetanib, reduces SARS-CoV-2 replication by inhibiting mitochondrial EGFR translocation and restoring mitochondrial function.

6) Vandetanib administration to SARS-CoV-2 infected mice alleviates viral load, clinical symptoms, and lung inflammation.
Vandetanib demonstrates potent antiviral activity in vitro against various SARS-CoV-2 variants including Alpha, Beta, Delta and Omicron.

7) The findings reveal a physiologically relevant role for SARS-CoV-2-induced changes in mitochondrial dynamics and EGFR signaling in supporting viral persistence. EGFR inhibitors may be promising therapeutic candidates for COVID-19.

Thanks for reading 🙏