Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 Feb 24;9(1):17.
doi: 10.3390/diseases9010017.

Involvement of Oxidative Stress and the Innate Immune System in SARS-CoV-2 Infection

Evgenii M Kozlov  1 , Ekaterina Ivanova  2 , Andrey V Grechko  3 , Wei-Kai Wu  4 , Antonina V Starodubova  5   6 , Alexander N Orekhov  7   8
Affiliations
Review

Involvement of Oxidative Stress and the Innate Immune System in SARS-CoV-2 Infection

Evgenii M Kozlov et al. Diseases. .

Abstract

The emergence of the novel coronavirus in December 2019 in China marked the beginning of a pandemic that impacted healthcare systems and economic life all over the world. The virus primarily targets the respiratory system causing severe acute respiratory syndrome (SARS) in some patients, and therefore received the name of SARS-CoV-2. The pathogen stands out among other coronaviruses by its rapid transmission from human to human, with the majority of infected individuals being asymptomatic or presenting with only minor illness, therefore facilitating the pathogen spread. At the same time, people from the risk groups, such as the elderly, patients suffering from chronic diseases, or obese individuals, have increased chances of developing a severe or even fatal disease. The search for risk factors explaining this phenomenon continues. In this review, we focus on the known mechanisms of SARS-CoV-2 infection affecting the functioning of the immune system and discuss potential risk factors responsible for the severe disease course. Oxidative stress is one of such factors, which plays a prominent role in innate immunity activity, and recent research has revealed its tight involvement in SARS-CoV-2 infection. We discuss these recent findings and the development of excessive inflammation and cytokine storm observed during SARS-CoV-2 infection. Finally, we consider potential use of antioxidant drugs for alleviating the severe symptoms in affected patients.

Keywords: SARS-CoV-2; innate immunity; macrophage; oxidative stress.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Possible ways of oxidative stress involvement in the COVID-19 disease. SARS-CoV-2 binds with ACE2 receptor; as a result, this virus enters into the host cells by endocytosis. The different virus components are recognized by PRR. For example, S-protein is distinguished by TLR2/4; ssRNA of coronavirus is distinguished by TLR7/8. Besides, RIG-I/MDA5 could identify dsRNA, a replication intermediate for RNA viruses. When sensing of dsRNA is performed, it leads to the cooperation with MAVS and further oligomerization process that attracts the adaptor proteins with subsequent activation of NF-κB and IRF factors. Also, viroporin E is capable of changing the ion flows of Ca2+ and K+ which drive to NALP3 activation. TLRs sensing provides the recruitment of adaptor proteins which can form the myddosome complex for NF-κB activation. NF-κB signaling is linked by expression of interleukin precursors. The activation effects on NALP3 inflammasome are necessary to realize the olizomerization process and ASC recruitment. Eventually, the formed inflammasome converts pro-caspase-1 to active caspase-1 in order to execute the processing of pro-interleukins. Stimulation of NF-κB signaling is associated with increasing of NOX expression, succeeded by ROS production. ROS can serve as signaling molecules that induce NF-κB signaling as well. Thus, the excessive ROS production mediates the hyper-inflammation and development of cytokine storm that impact both the possibility of ARDS development and severity of ARDS course.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Yeager C.L., Ashmun R.A., Williams R.K., Cardellichio C.B., Shapiro L.H., Look A.T., Holmes K.V. Human aminopeptidase N is a receptor for human coronavirus 229E. Nature. 1992;357:420–422. doi: 10.1038/357420a0. - DOI - PMC - PubMed
    1. Abdul-Rasool S., Fielding B.C. Understanding human coronavirus HCoV-NL63. Open Virol. J. 2010;4:76–84. doi: 10.2174/1874357901004010076. - DOI - PMC - PubMed
    1. Anderson R.M., Fraser C., Ghani A.C., Donnelly C.A., Riley S., Ferguson N.M., Leung G.M., Lam T.H., Hedley A.J. Epidemiology, transmission dynamics and control of SARS: The 2002–2003 epidemic. Philos. Trans. R. Soc. Lond. B Biol. Sci. 2004;359:1091–1105. doi: 10.1098/rstb.2004.1490. - DOI - PMC - PubMed
    1. Tong T.R. Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) Perspect. Med. Virol. 2006;16:43–95. doi: 10.1016/S0168-7069(06)16004-8. - DOI - PMC - PubMed
    1. Cherry J.D. The chronology of the 2002–2003 SARS mini pandemic. Paediatr. Respir. Rev. 2004;5:262–269. doi: 10.1016/j.prrv.2004.07.009. - DOI - PMC - PubMed

LinkOut - more resources