Hyperglycosylated spike of SARS-CoV-2 gamma variant induces breast cancer metastasis

SARS-CoV-2 exploits the host cellular machinery for virus replication leading to the acute syndrome of coronavirus disease 2019 (COVID-19). Growing evidence suggests SARS-CoV-2 also exacerbates many chronic diseases, including cancers. As mutations on the spike protein (S) emerged as dominant variants that reduce vaccine efficacy, little is known about the relation between SARS-CoV-2 virus variants and cancers. Compared to the SARS-CoV-2 wild-type, the Gamma variant contains two additional NXT/S glycosylation motifs on the S protein. The hyperglycosylated S of Gamma variant is more stable, resulting in more significant epithelial-mesenchymal transition (EMT) potential. SARS-CoV-2 infection promoted NF-kappa B signaling activation and p65 nuclear translocation, inducing Snail expression. Pharmacologic inhibition of NF-kappa B activity by nature food compound, 13C suppressed viral replication and Gamma variant-mediated breast cancer metastasis, indicating that NF-kappa B inhibition can reduce chronic disease in COVID-19 patients. Our study revealed that the Gamma variant of SARS-CoV-2 activates NF-kappa B and, in turn, triggers the pro-survival function for cancer progression.

Automated summary

An investigation found that the Gamma variant of SARS-CoV-2 activates NF-kappa B signaling, leading to pro-survival functions in cancer progression. Inhibiting NF-kappa B could reduce the risk of chronic diseases in COVID-19 patients.