Figure 3
Figure 3. SARS-CoV-2 entry and its possible influence on mitochondrial function in establishing Covid-19 infection. Upon SARS-CoV-2 entry, RNA genome is released and interact with various parts of mitochondria. ORF-9b localize the viral RNA genome in the host mitochondria as ORF-9b could facilitate the degradation of Dynamin related protein (Drp1) through ubiquitination. ORF-9b also manipulates the mitochondrial antiviral signaling (MAVS) protein through modulation of poly (C)-binding protein 2 (PCBP2) and a E3 Ubiquitin Protein Ligase, AIP4 to degrade MAVS and TNF Receptor Associated Factor (TRAF) 3 and 6, thereby limits INF production and host immunity. On the otherhand, ORFs7a and 8a may localize RNA genome to mitochondria, ORF3a may target mitochondrial ubiquitin specific peptidase 30 (USP30) and decrease mitophagy. Also, ORF9c and Nsp7 were predicted to interact with mitochondrial proteins NDUFAF1 and 2, respectively which may reduce complex I function, required for ROS and ATP production in immune signaling. Mitochondrial Tom 70 also shown to interact with SARS-CoV2- genome, in modulating antiviral cellular defense pathways. MtDNA released during these process may activate cytokine storm through cGAS/STING and NLRP3 pathways.