Roles of host mitochondria
in the development of COVID-19 pathology
Kavya Srinivasan1, 3, Ashutosh
Pandey2 and Sundararajan
Venkatesh1,*
1Department of Microbiology, Biochemistry and
Molecular Genetics, 2Department of Pharmacology,
Physiology and Neuroscience, Rutgers -New Jersey Medical School, The
State University of New Jersey, Newark, New Jersey, United States,3New York Institute of Technology, Old Westbury, New
York, United States.
*Corresponding author:
E-mail: sundarve@njms.rutgers.edu
Competing Interest: None
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). COVID-19 pathologies are currently under intense scrutiny as
its outbreak led to immense and urgent changes worldwide. Although many
theories have been introduced on how SARS-CoV-2 enters the host, the
ACE-2 receptor is shown to be the primary mechanism of SARS-CoV-2 entry.
However, the mechanism behind the establishment and pathology of
infection is poorly understood. As recent studies show that host
mitochondria play an essential role in virus-mediated innate immune
response, in this review, we will discuss, in detail, the entry and
progression of SARS-CoV-2 and how mitochondria play a role in the
establishment of viral infection and the development of an immune
response, whether it is beneficial or not. We will also review the
possible treatments that could be used to prevent the surgency of
COVID-19 infection with respect to the role of mitochondria.
Understanding the mitochondria-mediated SARS-CoV-2 establishment may
provide a unique mechanism and conceptual advancement in finding a novel
treatment for COVID-19.
KEYWORDS
COVID-19, SARS-CoV-2, Mitochondria, ORFs, ACE-2 receptor, Cytokine
storm, inflammation
INTRODUCTION
COVID-19 is caused by a new coronavirus identified as a severe acute
respiratory syndrome- coronavirus 2 (SARS-CoV-2), which has been
stirring the globe since the start of its outbreak in late 2019. At the
time of this draft submission, around ~90.7 million
people have been infected with SARS-CoV-2, and more than 1.9 million
died with a 2% death rate across the globe
(https://www.worldometers.info/coronavirus/). The only possible
prevention method so far is a combination of social distancing and
improved personal hygiene in addition to the current vaccine programs on
the roll. As cases continue to rise, there is an emergent need for
research concerning disease pathology as it is crucial to discovering
effective prevention and treatment of the disease. Like most notable
human disease-causing viruses, SARS-CoV-2 also contains positive
single-stranded RNA and belongs to a subgroup of the coronavirus family
known as beta-coronavirus. The other notable RNA viruses are those that
cause the common cold, dengue, Ebola, hepatitis C, hepatitis E,
influenza, measles, MERS, polio, rabies, SARS, and West Nile fever.
Among these, SARS-CoV-2 is more contagious than its counterparts because
this virus originated in animals and then transferred to humans at an
exceptionally high infection rate as our immune systems were never
exposed to this specific strain before. The infection is particularly
lethal in patients with compromised immunity and preexisting conditions.
Beta coronaviruses known to cause mild upper respiratory tract
infections include strains such as HCoV 229E, HKU1, NL63, and OC43 (Liu,
Liang & Fung, 2020). In contrast, the three strains that cause severe
life-threatening diseases are SARS-CoV, MERS-CoV, and the recently
identified SARS-CoV-2 (Memish, Zumla, Al-Hakeem, Al-Rabeeah & Stephens,
2013; Tiwari, Upadhyay, Nazam Ansari & Joshi, 2020; Zhu et al., 2020b).
Angiotensin-converting enzyme-2 (ACE-2) receptor-mediated entry of the
virus is considered the primary mechanism of infection; however, the
consequence of the entry and mechanisms of pathologies leading to
mortality, such as cytokine storm and inflammation, is unclear. Many
newfound studies suggest the potential involvement of host mitochondria
in COVID-19 infection, which is believed to be the key mechanism for
COVID-19 pathology (Edeas, Saleh & Peyssonnaux, 2020; Guzzi,
Mercatelli, Ceraolo & Giorgi, 2020; Kloc, Ghobrial & Kubiak, 2020;
Singh, Chaubey, Chen & Suravajhala, 2020). Therefore, in this review,
we seek more clarity surrounding mitochondria and their role in the
establishment of COVID-19 infection. We also discuss possible strategies
involving the use of mitochondria as potential therapeutic targets for
COVID-19.