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.