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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: 20 September 2024 | Viewed by 6421

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Prof. Dr. Marija S. Plješa-Ercegovac

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Guest Editor

Institute of Medical and Clinical Biochemistry, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia
Interests: oxidative stress; polymorphisms; glutathione transferases; urogenital cancers

Special Issue Information

Dear Colleagues,

It is well established that oxidative stress plays an important role in severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection. Indeed, significant alterations in redox homeostasis, due to altered antioxidant capacity, have been shown to contribute to the vicious cycle of inflammation and oxidative stress in COVID-19. Furthermore, oxidative stress and the impaired expression of antioxidant enzymes, as well as cytoprotective proteins under the control of the antioxidative response element in the DNA, have been suggested as the molecular basis of long-COVID. Since antioxidants have the ability to counteract the action of oxidants by scavenging reactive oxygen species (ROS) and by inhibiting oxidant-generating enzymes, various antioxidants have been proposed as “anti-SARS-CoV-2 agents”. However, further studies are needed to clarify the role of antioxidants as potential therapeutic strategies for both the prevention and treatment of acute COVID-19, as well as long-COVID.

Prof. Dr. Marija S. Plješa-Ercegovac
Guest Editor

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Keywords

antioxidants
COVID-19
oxidative stress
antioxidant capacity
long-COVID
vitamins

Published Papers (4 papers)

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Research

12 pages, 292 KiB

Open AccessArticle

GPX3 Variant Genotype Affects the Risk of Developing Severe Forms of COVID-19

by Marko Markovic, Jovan Ranin, Zoran Bukumiric, Djurdja Jerotic, Ana Savic-Radojevic, Marija Pljesa-Ercegovac, Tatjana Djukic, Marko Ercegovac, Milika Asanin, Ivana Milosevic, Goran Stevanovic, Tatjana Simic, Vesna Coric and Marija Matic

Int. J. Mol. Sci. 2023, 24(22), 16151; https://doi.org/10.3390/ijms242216151 - 10 Nov 2023

Cited by 1 | Viewed by 1045

Abstract

In SARS-CoV-2 infection, excessive activation of the immune system intensively increases reactive oxygen species levels, causing harmful hyperinflammatory and oxidative state cumulative effects which may contribute to COVID-19 severity. Therefore, we assumed that antioxidant genetic profile, independently and complemented with laboratory markers, modulates COVID-19 severity. The study included 265 COVID-19 patients. Polymorphism of GSTM1, GSTT1, Nrf2 rs6721961, GSTM3 rs1332018, GPX3 rs8177412, GSTP1 rs1695, GSTO1 rs4925, GSTO2 rs156697, SOD2 rs4880 and GPX1 rs1050450 genes was determined with appropriate PCR-based methods. Inflammation (interleukin-6, CRP, fibrinogen, ferritin) and organ damage (urea, creatinine, transaminases and LDH) markers, complete blood count and coagulation status (d-dimer, fibrinogen) were measured. We found significant association for COVID-19 progression for patients with lymphocytes below 1.0 × 10⁹/L (OR = 2.97, p = 0.002). Increased IL-6 and CRP were also associated with disease progression (OR = 8.52, p = 0.001, and OR = 10.97, p < 0.001, respectively), as well as elevated plasma AST and LDH (OR = 2.25, p = 0.021, and OR = 4.76, p < 0.001, respectively). Of all the examined polymorphisms, we found significant association with the risk of developing severe forms of COVID-19 for GPX3 rs8177412 variant genotype (OR = 2.42, p = 0.032). This finding could be of particular importance in the future, complementing other diagnostic tools for prediction of COVID-19 disease course. Full article

(This article belongs to the Special Issue Focus on Antioxidants and COVID-19)

22 pages, 5153 KiB

Open AccessArticle

Pharmacogenomic Landscape of Ivermectin and Selective Antioxidants: Exploring Gene Interplay in the Context of Long COVID

by Ying-Fei Yang and Sher Singh

Int. J. Mol. Sci. 2023, 24(20), 15471; https://doi.org/10.3390/ijms242015471 - 23 Oct 2023

Cited by 1 | Viewed by 2079

Abstract

COVID-19 pandemic has caused widespread panic and fear among the global population. As such, repurposing drugs are being used as viable therapeutic options due to the limited effective treatments for Long COVID symptoms. Ivermectin is one of the emerging repurposed drugs that has been shown effective to have antiviral effects in clinical trials. In addition, antioxidant compounds are also gaining attention due to their capabilities of reducing inflammation and severity of symptoms. Due to the absence of knowledge in pharmacogenomics and modes of actions in the human body for these compounds, this study aims to provide a pharmacogenomic profile for the combination of ivermectin and six selected antioxidants (epigallocatechin gallate (EGCG), curcumin, sesamin, anthocyanins, quercetin, and N-acetylcysteine (NAC)) as potentially effective regimens for long COVID symptoms. Results showed that there were 12 interacting genes found among the ivermectin, 6 antioxidants, and COVID-19. For network pharmacology, the 12 common interacting genes/proteins had the highest associations with Pertussis pathway, AGE-RAGE signaling pathway in diabetic complications, and colorectal cancer in the Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Disease analyses also revealed that the top three relevant diseases with COVID-19 infections were diabetes mellitus, ischemia, reperfusion injury. We also identified 6 potential target microRNAs (miRNAs) of the 12 commonly curated genes used as molecular biomarkers for COVID-19 treatments. The established pharmacogenomic network, disease analyses, and identified miRNAs could facilitate developments of effective regimens for chronic sequelae of COVID-19 especially in this post-pandemic era. However, further studies and clinical trials are needed to substantiate the effectiveness and dosages for COVID-19 treatments. Full article

(This article belongs to the Special Issue Focus on Antioxidants and COVID-19)

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13 pages, 4048 KiB

Open AccessArticle

Improving Soluble Expression of SARS-CoV-2 Spike Priming Protease TMPRSS2 with an Artificial Fusing Protein

by Xiao Ye, Xue Ling, Min Wu, Guijie Bai, Meng Yuan and Lang Rao

Int. J. Mol. Sci. 2023, 24(13), 10475; https://doi.org/10.3390/ijms241310475 - 22 Jun 2023

Viewed by 1585

Abstract

SARS-CoV-2 relies on the recognition of the spike protein by the host cell receptor ACE2 for cellular entry. In this process, transmembrane serine protease 2 (TMPRSS2) plays a pivotal role, as it acts as the principal priming agent catalyzing spike protein cleavage to initiate the fusion of the cell membrane with the virus. Thus, TMPRSS2 is an ideal pharmacological target for COVID-19 therapy development, and the effective production of high–quality TMPRSS2 protein is essential for basic and pharmacological research. Unfortunately, as a mammalian–originated protein, TMPRSS2 could not be solubly expressed in the prokaryotic system. In this study, we applied different protein engineering methods and found that an artificial protein XXA derived from an antifreeze protein can effectively promote the proper folding of TMPRSS2, leading to a significant improvement in the yield of its soluble form. Our study also showed that the fused XXA protein did not influence the enzymatic catalytic activity; instead, it greatly enhanced TMPRSS2′s thermostability. Therefore, our strategy for increasing TMPRSS2 expression would be beneficial for the large–scale production of this stable enzyme, which would accelerate aniti–SARS-CoV-2 therapeutics development. Full article

(This article belongs to the Special Issue Focus on Antioxidants and COVID-19)

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14 pages, 2217 KiB

Open AccessArticle

Antioxidant Genetic Variants Modify Echocardiography Indices in Long COVID

by Milika Asanin, Marko Ercegovac, Gordana Krljanac, Tatjana Djukic, Vesna Coric, Djurdja Jerotic, Marija Pljesa-Ercegovac, Marija Matic, Ivana Milosevic, Mihajlo Viduljevic, Goran Stevanovic, Jovan Ranin, Tatjana Simic, Zoran Bukumiric and Ana Savic-Radojevic

Int. J. Mol. Sci. 2023, 24(12), 10234; https://doi.org/10.3390/ijms241210234 - 16 Jun 2023

Cited by 2 | Viewed by 1234

Abstract

Although disturbance of redox homeostasis might be responsible for COVID-19 cardiac complications, this molecular mechanism has not been addressed yet. We have proposed modifying the effects of antioxidant proteins polymorphisms (superoxide dismutase 2 (SOD2), glutathione peroxidase 1 (GPX1), glutathione peroxidase 3 (GPX3) and nuclear factor erythroid 2-related factor 2, (Nrf2)) in individual susceptibility towards the development of cardiac manifestations of long COVID-19. The presence of subclinical cardiac dysfunction was assessed via echocardiography and cardiac magnetic resonance imaging in 174 convalescent COVID-19 patients. SOD2, GPX1, GPX3 and Nrf2 polymorphisms were determined via the appropriate PCR methods. No significant association of the investigated polymorphisms with the risk of arrhythmia development was found. However, the carriers of variant GPX1*T, GPX3*C or Nrf2*A alleles were more than twice less prone for dyspnea development in comparison with the carriers of the referent ones. These findings were even more potentiated in the carriers of any two variant alleles of these genes (OR = 0.273, and p = 0.016). The variant GPX alleles were significantly associated with left atrial and right ventricular echocardiographic parameters, specifically LAVI, RFAC and RV-EF (p = 0.025, p = 0.009, and p = 0.007, respectively). Based on the relation between the variant SOD2*T allele and higher levels of LV echocardiographic parameters, EDD, LVMI and GLS, as well as troponin T (p = 0.038), it can be proposed that recovered COVID-19 patients, who are the carriers of this genetic variant, might have subtle left ventricular systolic dysfunction. No significant association between the investigated polymorphisms and cardiac disfunction was observed when cardiac magnetic resonance imaging was performed. Our results on the association between antioxidant genetic variants and long COVID cardiological manifestations highlight the involvement of genetic propensity in both acute and long COVID clinical manifestations. Full article

(This article belongs to the Special Issue Focus on Antioxidants and COVID-19)

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