Mitochondria Targeted Viral Replication and Survival Strategies—Prospective on SARS-CoV-2

Abstract

SARS-CoV-2 is a positive sense RNA coronavirus that constitutes a new threat for the global community and economy. While vaccines against SARS-CoV-2 are being developed, the mechanisms through which this virus takes control of an infected cell to replicate remains poorly understood. Upon infection, viruses completely rely on host cell molecular machinery to survive and replicate. To escape from the immune response and proliferate, viruses strategically modulate cellular metabolism and alter subcellular organelle architecture and functions. One way they do this is by modulating the structure and function of mitochondria, a critical cellular metabolic hub but also a key platform for the regulation of cellular immunity. This versatile nature of mitochondria defends host cells from viruses through several mechanisms including cellular apoptosis, ROS signaling, MAVS activation and mitochondrial DNA-dependent immune activation. These events are regulated by mitochondrial dynamics, a process by which mitochondria alter their structure (including their length and connectivity) in response to stress or other cues. It is therefore not surprising that viruses, including coronaviruses hijack these processes for their survival. In this review, we highlight how positive sense RNA viruses modulate mitochondrial dynamics and metabolism to evade mitochondrial mediated immune response in order to proliferate.

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“…Moreover, over-expression of the M protein results in down-regulation of Akt phosphorylation as shown in Fig. 1, which reducing cell survival signal and induced apoptosis; additionally, mislocalization of mitochondrial cytochrome C and nuclear condensation was observed in M-expressing cells [38][39] .…”

Mitochondria as Targets for Endothelial Protection in COVID-19

“…Downstream IFN-I signaling involves mitochondrial adapters MAVS/TOM70/TRAF3/TRAF6 attached to the outer mitochondrial membrane at the contact sites with the endoplasmic reticulum (the so-called mitochondria-associated membranes, MAMs). IFN-I signaling and various anti-IFN strategies of positive-sense RNA viruses including coronaviruses have recently been extensively reviewed (Gatti et al, 2020).…”

“…It was predicted that some other SARS-CoV-2 proteins interfere with IFN-I signaling and interact with the mitochondrial respiratory chain, the protein import machinery, and ribosomes (Gatti et al, 2020;Gordon et al, 2020). These interactions may promote viral replication by modulating mitochondrial metabolism and/or preventing the early induction of apoptosis (Gatti et al, 2020). At the later stages of infection, these proteins may stimulate cell death, helping viral dissemination.…”

Potential roles of mitochondrial cofactors in the adjuvant mitigation of proinflammatory acute infections, as in the case of sepsis and COVID-19 pneumonia

“…The relationship between OS and the risk of death in patients infected with COVID-19 suggests the need for alternative approaches to counteract this infection [ 28 ]. In addition, a recent report on the possible participation of COVID-19 in weakening mitochondrial functions suggests the need to consider these organelles as an object for adjuvant therapeutic effects targetting [ 16 , 17 , 29 , 30 ].…”