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J Med Virol . SARS-CoV-2 nucleocapsid protein enhances the level of mitochondrial reactive oxygen species

tetano

Editor, Senior Moderator
J Med Virol


. 2023 Dec;95(12):e29270.
doi: 10.1002/jmv.29270. SARS-CoV-2 nucleocapsid protein enhances the level of mitochondrial reactive oxygen species

Haiyun Yu[SUP] 1 [/SUP], Lu Yang[SUP] 1 [/SUP], Zhennan Han[SUP] 1 [/SUP], Xiaoyu Zhou[SUP] 1 [/SUP], Zihan Zhang[SUP] 1 [/SUP], Tianli Sun[SUP] 1 [/SUP], Fang Zheng[SUP] 2 [/SUP], Jingzhi Yang[SUP] 3 [/SUP], Fei Guan[SUP] 1 [/SUP], Jungang Xie[SUP] 4 [/SUP], Chaohong Liu[SUP] 1 [/SUP]



Affiliations
Abstract

Coronavirus disease 2019 (COVID-19) pathogenesis is influenced by reactive oxygen species (ROS). Nevertheless, the precise mechanisms implicated remain poorly understood. The nucleocapsid (N) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the main driver for this condition, is a structural protein indispensable for viral replication and assembly, and its role in ROS production has not been reported. This study shows that SARS-CoV-2 N protein expression enhances mitochondrial ROS level. Bulk RNA-sequencing suggests of aberrant redox state of the electron transport chain. Accordingly, this protein hinders ATP production but simultaneously augments the activity of complexes I and III, and most mitochondrially encoded complex I and III proteins are upregulated by it. Mechanistically, N protein of SARS-CoV-2 shows significant mitochondrial localization. It interacts with mitochondrial transcription components and stabilizes them. Moreover, it also impairs the activity of antioxidant enzymes with or without detectable interaction.

Keywords: ROS; SARS-CoV-2; interaction; mitochondria; nucleocapsid.

 
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