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.