A Review of the Potential Roles of Antioxidant and Anti-Inflammatory Pharmacological Approaches for the Management of Mild-to-Moderate Symptomatic COVID-19

Overview

Journal Med Sci Monit

Specialties General Medicine
Pathology

Date 2022 Mar 8

PMID 35256581

Authors

Serafino Fazio

Flora Affuso

Paolo Bellavite

Affiliations

Soon will be listed here.

Abstract

In the past 2 years, the coronavirus disease 2019 (COVID-19) pandemic has driven investigational studies and controlled clinical trials on antiviral treatments and vaccines that have undergone regulatory approval. Now that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants may become endemic over time, there remains a need to identify drugs that treat the symptoms of COVID-19 and prevent progression toward severe cases, hospitalization, and death. Understanding the molecular mechanisms of SARS-CoV-2 infection is extremely important for the development of effective therapies against COVID-19. This review outlines the key pathways involved in the host response to SARS-CoV-2 infection and discusses the potential role of antioxidant and anti-inflammatory pharmacological approaches for the management of early mild-to-moderate COVID-19, using the examples of combined indomethacin, low-dose aspirin, omeprazole, hesperidin, quercetin, and vitamin C. The pharmacological targets of these substances are described here for their possible synergism in counteracting SARS-CoV-2 replication and progression of the infection from the upper respiratory airways to the blood, avoiding vascular complications and cytokine and bradykinin storms.

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References

Okoli G, Rabbani R, Al-Juboori A, Copstein L, Askin N, Abou-Setta A . Antiviral drugs for coronavirus disease 2019 (COVID-19): a systematic review with network meta-analysis. Expert Rev Anti Infect Ther. 2021; 20(2):267-278. PMC: 8477589. DOI: 10.1080/14787210.2021.1961579. View

Checconi P, De Angelis M, Marcocci M, Fraternale A, Magnani M, Palamara A . Redox-Modulating Agents in the Treatment of Viral Infections. Int J Mol Sci. 2020; 21(11). PMC: 7312898. DOI: 10.3390/ijms21114084. View

Liu Q, Huang N, Li A, Zhou Y, Liang L, Song X . Effect of low-dose aspirin on mortality and viral duration of the hospitalized adults with COVID-19. Medicine (Baltimore). 2021; 100(6):e24544. PMC: 7886487. DOI: 10.1097/MD.0000000000024544. View

Guazelli C, Fattori V, R Ferraz C, Borghi S, Casagrande R, Baracat M . Antioxidant and anti-inflammatory effects of hesperidin methyl chalcone in experimental ulcerative colitis. Chem Biol Interact. 2020; 333:109315. DOI: 10.1016/j.cbi.2020.109315. View

Zhang X, Wu X, Hu Q, Wu J, Wang G, Hong Z . Mitochondrial DNA in liver inflammation and oxidative stress. Life Sci. 2019; 236:116464. DOI: 10.1016/j.lfs.2019.05.020. View

Parhiz H, Roohbakhsh A, Soltani F, Rezaee R, Iranshahi M . Antioxidant and anti-inflammatory properties of the citrus flavonoids hesperidin and hesperetin: an updated review of their molecular mechanisms and experimental models. Phytother Res. 2014; 29(3):323-31. DOI: 10.1002/ptr.5256. View

Schroer J, Shenk T . Inhibition of cyclooxygenase activity blocks cell-to-cell spread of human cytomegalovirus. Proc Natl Acad Sci U S A. 2008; 105(49):19468-73. PMC: 2614784. DOI: 10.1073/pnas.0810740105. View

Shovlin C, Vizcaychipi M . Vascular inflammation and endothelial injury in SARS-CoV-2 infection: the overlooked regulatory cascades implicated by the ACE2 gene cluster. QJM. 2020; 116(8):629-634. PMC: 7454888. DOI: 10.1093/qjmed/hcaa241. View

Russo M, Moccia S, Spagnuolo C, Tedesco I, Russo G . Roles of flavonoids against coronavirus infection. Chem Biol Interact. 2020; 328:109211. PMC: 7385538. DOI: 10.1016/j.cbi.2020.109211. View

10.

Wang X, Yang C, Sun Y, Sui X, Zhu T, Wang Q . A novel screening strategy of anti-SARS-CoV-2 drugs via blocking interaction between Spike RBD and ACE2. Environ Int. 2021; 147:106361. PMC: 7832953. DOI: 10.1016/j.envint.2020.106361. View

11.

Watzky M, de Dieuleveult M, Letessier A, Saint-Ruf C, Miotto B . Assessing the consequences of environmental exposures on the expression of the human receptor and proteases involved in SARS-CoV-2 cell-entry. Environ Res. 2020; 195:110317. PMC: 7560643. DOI: 10.1016/j.envres.2020.110317. View

12.

Conti P, Caraffa A, Tete G, Gallenga C, Ross R, Kritas S . Mast cells activated by SARS-CoV-2 release histamine which increases IL-1 levels causing cytokine storm and inflammatory reaction in COVID-19. J Biol Regul Homeost Agents. 2020; 34(5):1629-1632. DOI: 10.23812/20-2EDIT. View

13.

Wu C, Liu Y, Yang Y, Zhang P, Zhong W, Wang Y . Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods. Acta Pharm Sin B. 2020; 10(5):766-788. PMC: 7102550. DOI: 10.1016/j.apsb.2020.02.008. View

14.

Fogari R, Zoppi A, Tettamanti F, Malamani G, Tinelli C, Salvetti A . Effects of nifedipine and indomethacin on cough induced by angiotensin-converting enzyme inhibitors: a double-blind, randomized, cross-over study. J Cardiovasc Pharmacol. 1992; 19(5):670-3. View

15.

Shekhar N, Kaur H, Sarma P, Prakash A, Medhi B . Indomethacin: an exploratory study of antiviral mechanism and host-pathogen interaction in COVID-19. Expert Rev Anti Infect Ther. 2021; 20(3):383-390. PMC: 8544661. DOI: 10.1080/14787210.2022.1990756. View

16.

Ho P, Zheng J, Wu C, Hou Y, Liu W, Lu C . Perspective Adjunctive Therapies for COVID-19: Beyond Antiviral Therapy. Int J Med Sci. 2021; 18(2):314-324. PMC: 7757136. DOI: 10.7150/ijms.51935. View

17.

Amani B, Khanijahani A, Amani B . Hydroxychloroquine plus standard of care compared with standard of care alone in COVID-19: a meta-analysis of randomized controlled trials. Sci Rep. 2021; 11(1):11974. PMC: 8184930. DOI: 10.1038/s41598-021-91089-3. View

18.

Potus F, Mai V, Lebret M, Malenfant S, Breton-Gagnon E, Lajoie A . Novel insights on the pulmonary vascular consequences of COVID-19. Am J Physiol Lung Cell Mol Physiol. 2020; 319(2):L277-L288. PMC: 7414237. DOI: 10.1152/ajplung.00195.2020. View

19.

Bonaventura A, Vecchie A, Dagna L, Martinod K, Dixon D, Van Tassell B . Endothelial dysfunction and immunothrombosis as key pathogenic mechanisms in COVID-19. Nat Rev Immunol. 2021; 21(5):319-329. PMC: 8023349. DOI: 10.1038/s41577-021-00536-9. View

20.

Herrera D, Serrano J, Roldan S, Sanz M . Is the oral cavity relevant in SARS-CoV-2 pandemic?. Clin Oral Investig. 2020; 24(8):2925-2930. PMC: 7309196. DOI: 10.1007/s00784-020-03413-2. View