The impact of oxidative stress damage induced by the environmental stressors on COVID-19

Abstract

The ongoing pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a substantial stressor that is greatly impacting environmental sustainability. Besides, the different pre-existing environmental stressors and coronavirus disease-2019 (COVID-19)-related stressors are further worsening the effects of the viral disease by inducing the generation of oxidative stress. The generated oxidative stress results in nucleic acid damage associated with viral mutations, that could potentially reduce the effectiveness of COVID-19 management, including the vaccine approach. The current review is aimed to overview the impact of the oxidative stress damage induced by various environmental stressors on COVID-19. The available data regarding the COVID-19-related stressors and the effects of oxidative stress damage induced by the chronic stress, exposure to free radicals, and malnutrition are also analyzed to showcase the promising options, which could be investigated further for sustainable control of the pandemic.

Keywords: COVID-19; Chronic stress; Environmental stressors; Oxidative stress damage; Vaccine; Viral mutations.

Graphical abstract

Fig. 1

Chronic stress could stimulate CTRA via the sympathetic nervous system leading to the induction of proinflammatory cytokines and suppression of genes involved in the production of antibodies and interferons, resulting in the vulnerability of viral infections. Proinflammatory cytokines induce chronic inflammation and ROS generation, thus producing an imbalanced oxidative stress response. The latter induces oxidative damage of endogenous molecules (nucleic acids, lipids, proteins), resulting in DAMPS that cause proinflammatory cytokine secretion (cytokine storm). For a person infected with a virus such as SARS-CoV-2, oxidative damage may result in viral mutations that could result in minimizing the effect of the immune system and vaccine. Besides, the overproduction of ROS suppresses the T lymphocyte response, which results in impaired adaptive immunity. CTRA, conserved transcriptional response to adversity; IFN, interferon; ROS, reactive oxygen species; Abs, antibodies; DAMPS, damage-associated molecular patterns; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.

Fig. 2

Origin of reactive oxygen and reactive nitrogen species. These can be from endogenous sources such as mental stress, metabolism, and inflammation as well as exogenous sources such as poor diet, UV radiation, ionizing radiation, and atmospheric pollution. When these exogenous compounds penetrate the body, these are degraded or metabolized, resulting in the generation of ROS and RNS as the byproducts. OH•, hydroxyl radical; O₂•⁻, superoxide anion; H₂O₂, hydrogen peroxide; NO•, nitric oxide radical; •NO₃, peroxynitrite; •NO₂, nitrogen dioxide; cysp, cyclosporine; Tac, tacrolimus; Gen, gentamycin; BLM, bleomycin; Dox, doxorubicin; AZT, azidothymidine; Dic, diclofenac; PCM, paracetamol; Cis, cisplatin; CP, chlorpromazine.

Fig. 3

Mode of action of the main antioxidant enzymatic systems and their metal cofactors. CuZn, copper-zinc; Mn, manganese; Se, selenium; Fe, iron; Cu, copper.

Fig. 4

SARS-CoV-2 replication in the presence of oxidative stress. SARS-CoV-2 infects the host cell through interactions between its spike protein (S) and cell receptor, ACE2. The release of viral RNA through endosomes into the cytoplasm in the presence of oxidative stress may result in RNA mutation. After ARN mutation, the translation of viral polyprotein followed by proteolysis produces non-structural proteins (NSPs) and forms replication-transcription complex (RTC). The RTC drives the synthesis of (−) RNA. Full length (−) RNA copies of the genome provide templates for full-length (+) RNA genomes. Transcription further produces a subset of subgenomic RNAs, including those encoding the accessory and structural proteins. The oxidative stress may act on proteins resulting from the translation of messenger RNAs and could completely change the structure of the virus. The translated structural proteins (M, N, E, S) and genomic RNA are assembled into the viral nucleocapsid and envelope in the ER-Golgi intermediate compartment, which are subsequently released via exocytosis. The SARS-CoV-2 mutant would escape the antibody immune response. SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; ACE2, angiotensin-converting enzyme 2; RNA, ribonucleic acid; (+) RNA, Positive-strand (5′-to-3′) RNA; (−) RNA, negative-strand (3′-to-5′) RNA; OH•, hydroxyl radical; O₂⁻•, superoxide anion; H₂O₂, hydrogen peroxide; NO•, nitrogen monoxide; N, nucleocapsid protein; M, matrix protein; E, envelope protein; S, spike protein.