SARS-CoV-2 might manipulate against its host the immunity RNAi/Dicer/Ago system Does mitochondria collapse upon COVID-19 infection?

Claude Pasquier; Alain Robichon

RISC/Ago might be fueled by diverse source of RNAi, byproducts of the action of Dicer, originated from hybrid and asymmetric RNA duplex, one strand coming from host and the other from the virus. Our conclusions reside in the fact that i) intra or inter matching within the 5 coronaviruses are rare, ii) the list of hybrid duplex was significantly more important in SARS-CoV-2 than in the other strands, iii) regarding SARS-CoV-2, amazingly, hybrid duplexing sequences were found in three important human genes: mitochondrial ubiquitin specific peptidase 30 (USP30), a subunit of ubiquitin ligase complex (FBXO21) and finally ubiquitin specific peptidase 31 (USP31). USP 30 is a mitochondrial deubiquitinase involved in mitochondria homeostasis functions, one of which being to counter the Parkin mediated mitophagy [15] . USP 31 is known to increase the activity of the transcription factor NF kappa B (NF-kB), strongly involved in interferon (IFN) synthesis [16] . Interestingly, mitochondria shelter MAVS (mitochondrial antiviral signaling proteins), known to stimulate an interferon-dependent signaling pathway which orchestrate antiviral response in mammals [17] . SARS-CoV-2 might affect mitochondria via ubiquitination alteration, which could be a plausible pathway of interference to explain the dramatic deteriorating conditions of some patients affected by this virus.