Roles of host mitochondria in the development of COVID-19 pathology: Could mitochondria be a potential therapeutic target?

Abstract

The recent emergence of severe acute respiratory syndrome-Corona Virus 2 (SARS-CoV-2) in late 2019 and its spread worldwide caused an acute pandemic of Coronavirus disease 19 (COVID-19). Since then, COVID-19 has been under intense scrutiny as its outbreak led to significant changes in healthcare, social activities, and economic settings worldwide. Although angiotensin-converting enzyme-2 (ACE-2) receptor is shown to be the primary port of SARS-CoV-2 entry in cells, the mechanisms behind the establishment and pathologies of COVID-19 are poorly understood. As recent studies have shown that host mitochondria play an essential role in virus-mediated innate immune response, pathologies, and infection, in this review, we will discuss in detail the entry and progression of SARS-CoV-2 and how mitochondria could play roles in COVID-19 disease. We will also review the potential interactions between SARS-CoV-2 and mitochondria and discuss possible treatments, including whether mitochondria as a potential therapeutic target in COVID-19. Understanding SARS-CoV-2 and mitochondrial interactions mediated virus establishment, inflammation, and other consequences may provide a unique mechanism and conceptual advancement in finding a novel treatment for COVID-19.

Transcriptomic profiling of cardiac tissues from SARS-CoV-2 patients identifies DNA damage

“…For example, viral open reading frame 9c (ORF9c) interacts with NDUFAF1 and NDUFAB1 73,74 , genes we identified in our study that are required for cellular bioenergetics as part of Complex I. Indeed, SARS-CoV-2 manipulation of mitochondrial activity is likely to enable evasion of mitochondrial-mediated innate immunity 74,75 .…”

Exploring Mitochondrial Localization of SARS-CoV-2 RNA by Padlock Assay: A Pilot Study in Human Placenta

“…For our study, we took advantage of an archival FFPE tissue of the placenta from a pregnant woman with COVID-19. Contextually, we focused on placental mitochondria keeping in mind that increasing evidence points to the mitochondrion as an attractive target for both maintaining pregnancy and the SARS-CoV-2 life cycle [7][8][9]. Overall, to propagate itself and evade immune response, positive-sense RNA virus is prone to target mitochondrial dynamics [10,11].…”

Human Cell Organelles in SARS-CoV-2 Infection: An Up-to-Date Overview

“…In SARS-CoV-2 virus, various open reading frames (ORF), a genome sequence between the starting and ending codon which produces a functioning protein, have been found to interact with the host cell, specifically mitochondria, in order to alter its metabolism for viral infection. These proteins, grouped by the ORF that they come from, induce various changes in a host cell resulting in mitochondrial disruption [ 183 ]. Gordon et al have successfully cloned and expressed most of the SARS-CoV-2 proteins.…”

“…Additionally, ORFs help avoid instant response from antiviral mechanisms. They intensify the inflammation state and slow down the response, causing the cytokine storm [ 183 ]. This process reprograms host cell metabolism into the lycolysis cycle, lowering the ATP produced by the Krebs cycle and inducing mitochondrial atrophy [ 197 ].…”