1. Academic Validation
  2. Irradiation accelerates SARS-CoV-2 infection by enhancing sphingolipid metabolism

Irradiation accelerates SARS-CoV-2 infection by enhancing sphingolipid metabolism

  • J Med Virol. 2022 Nov 1;e28266. doi: 10.1002/jmv.28266.
Zhuanzhuan Wei 1 Yiyi Jiang 1 Gaomei Zhao 1 Chenwenya Li 1 Songling Han 1 Yin Chen 1 Tao Wang 1 Tianmin Cheng 1 Junping Wang 1 Cheng Wang 1


  • 1 State Key Laboratory of Trauma, Burns and Combined Injury, Chongqing Engineering Research Center for Nanomedicine, Institute of Combined Injury of PLA, College of Preventive Medicine, Third Military Medical University, Chongqing, China.

Cancer patients who receive radiotherapy have a high risk of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) Infection, but the concrete reason remains unclear. Herein, we investigated the influence of irradiation on the vulnerability of Cancer cells to SARS-CoV-2 using S pseudovirions and probed the underlying mechanism via RNA-seq and other Molecular Biology techniques. Owing to the enhancement of sphingolipid metabolism, irradiation accelerated pseudovirion Infection. Mechanistically, irradiation induced the expression of acid sphingomyelinase (ASM), which catalyses the hydrolysis of sphingomyelin to ceramide, contributing to lipid raft formation and promoting SARS-CoV-2 invasion. Inhibition of lipid raft formation with methyl-β-cyclodextrin (MβCD) or the tyrosine kinase inhibitor genistein and ASM suppression through small interfering RNA or amitriptyline (AMT) treatment abolished the enhancing effect of irradiation on viral Infection. Animal experiments supported the finding that irradiation promoted SARS-CoV-2 S pseudovirion Infection in A549 cell tumour-bearing BALB/c nude mice, whereas AMT treatment dramatically decreased viral Infection. This study discloses the role of sphingolipid metabolism in irradiation-induced SARS-CoV-2 Infection, thus providing a potential target for clinical intervention to protect patients receiving radiotherapy from COVID-19.


SARS-CoV-2; acid sphingomyelinase; amitriptyline; ceramide; irradiation.