Pathophysiological involvement of host mitochondria in SARS-CoV-2 infection that causes COVID-19: a comprehensive evidential insight.

Abstract

SARS-CoV-2 is a positive-strand RNA virus that infects humans through the nasopharyngeal and oral route causing COVID-19. Scientists left no stone unturned to explore a targetable key player in COVID-19 pathogenesis against which therapeutic interventions can be initiated. This article has attempted to review, coordinate and accumulate the most recent observations in support of the hypothesis predicting the altered state of mitochondria concerning mitochondrial redox homeostasis, inflammatory regulations, morphology, bioenergetics and antiviral signalling in SARS-CoV-2 infection. Mitochondria is extremely susceptible to physiological as well as pathological stimuli, including viral infections. Recent studies suggest that SARS-CoV-2 pathogeneses alter mitochondrial integrity, in turn mitochondria modulate cellular response against the infection. SARS-CoV-2M protein inhibited mitochondrial antiviral signalling (MAVS) protein aggregation in turn hinders innate antiviral response. Viral open reading frames (ORFs) also play an instrumental role in altering mitochondrial regulation of immune response. Notably, ORF-9b and ORF-6 impair MAVS activation. In aged persons, the NLRP3 inflammasome is over-activated due to impaired mitochondrial function, increased mitochondrial reactive oxygen species (mtROS), and/or circulating free mitochondrial DNA, resulting in a hyper-response of classically activated macrophages. This article also tries to understand how mitochondrial fission-fusion dynamics is affected by the virus. This review comprehends the overall mitochondrial attribute in pathogenesis as well as prognosis in patients infected with COVID-19 taking into account pertinent in vitro, pre-clinical and clinical data encompassing subjects with a broad range of severity and morbidity. This endeavour may help in exploring novel non-canonical therapeutic strategies to COVID-19 disease and associated complications.