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      Role of specialized pro-resolving lipid mediators and their receptors in virus infection: a promising therapeutic strategy for SARS-CoV-2 cytokine storm

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          Abstract

          Unexpected viral infections outbreaks, significantly affect human health, leading to increased mortality and life disruption. Among them is the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which emerged as a deadly pandemic, calling for intense research efforts on its pathogenicity mechanism and development of therapeutic strategies. In the SARS-CoV-2 cytokine storm, systemic inflammation has been associated with severe illness and mortality. Recent studies have demonstrated special pro-resolving lipids mediators (SPMs) lipoxins, resolvins, maresins, and protectins as potential therapeutic options for abnormal viral-triggered inflammation. Pro-resolving lipids mediators have shown great promise for the treatment of Herpes simplex virus, respiratory syncytial virus, human immunodeficiency virus, and hepatitis C virus. Based on this, studies are being conducted on their therapeutic effects in SARS-CoV-2 infection. In this review, we discussed SPMs and reviewed evidence from recent studies on SPMs as therapeutic options for viral infections, including SARS-CoV2. Based on our analysis of the previous study, we argue that SPMs are a potential treatment for SARS-CoV-2 infection and other viral infections. We expect further research on how SPMs modulate viral-triggered inflammation through G-protein-coupled receptors (GPCRs), and chemical stability and druggability of SPMs.

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          Most cited references134

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          Is Open Access

          The species Severe acute respiratory syndrome-related coronavirus : classifying 2019-nCoV and naming it SARS-CoV-2

          The present outbreak of a coronavirus-associated acute respiratory disease called coronavirus disease 19 (COVID-19) is the third documented spillover of an animal coronavirus to humans in only two decades that has resulted in a major epidemic. The Coronaviridae Study Group (CSG) of the International Committee on Taxonomy of Viruses, which is responsible for developing the classification of viruses and taxon nomenclature of the family Coronaviridae, has assessed the placement of the human pathogen, tentatively named 2019-nCoV, within the Coronaviridae. Based on phylogeny, taxonomy and established practice, the CSG recognizes this virus as forming a sister clade to the prototype human and bat severe acute respiratory syndrome coronaviruses (SARS-CoVs) of the species Severe acute respiratory syndrome-related coronavirus, and designates it as SARS-CoV-2. In order to facilitate communication, the CSG proposes to use the following naming convention for individual isolates: SARS-CoV-2/host/location/isolate/date. While the full spectrum of clinical manifestations associated with SARS-CoV-2 infections in humans remains to be determined, the independent zoonotic transmission of SARS-CoV and SARS-CoV-2 highlights the need for studying viruses at the species level to complement research focused on individual pathogenic viruses of immediate significance. This will improve our understanding of virus–host interactions in an ever-changing environment and enhance our preparedness for future outbreaks.
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            Novel Functional Sets of Lipid-Derived Mediators with Antiinflammatory Actions Generated from Omega-3 Fatty Acids via Cyclooxygenase 2–Nonsteroidal Antiinflammatory Drugs and Transcellular Processing

            Aspirin therapy inhibits prostaglandin biosynthesis without directly acting on lipoxygenases, yet via acetylation of cyclooxygenase 2 (COX-2) it leads to bioactive lipoxins (LXs) epimeric at carbon 15 (15-epi-LX, also termed aspirin-triggered LX [ATL]). Here, we report that inflammatory exudates from mice treated with ω-3 polyunsaturated fatty acid and aspirin (ASA) generate a novel array of bioactive lipid signals. Human endothelial cells with upregulated COX-2 treated with ASA converted C20:5 ω-3 to 18R-hydroxyeicosapentaenoic acid (HEPE) and 15R-HEPE. Each was used by polymorphonuclear leukocytes to generate separate classes of novel trihydroxy-containing mediators, including 5-series 15R-LX5 and 5,12,18R-triHEPE. These new compounds proved to be potent inhibitors of human polymorphonuclear leukocyte transendothelial migration and infiltration in vivo (ATL analogue > 5,12,18R-triHEPE > 18R-HEPE). Acetaminophen and indomethacin also permitted 18R-HEPE and 15R-HEPE generation with recombinant COX-2 as well as ω-5 and ω-9 oxygenations of other fatty acids that act on hematologic cells. These findings establish new transcellular routes for producing arrays of bioactive lipid mediators via COX-2–nonsteroidal antiinflammatory drug–dependent oxygenations and cell–cell interactions that impact microinflammation. The generation of these and related compounds provides a novel mechanism(s) for the therapeutic benefits of ω-3 dietary supplementation, which may be important in inflammation, neoplasia, and vascular diseases.
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              Resolution of inflammation: a new therapeutic frontier.

              Dysregulated inflammation is a central pathological process in diverse disease states. Traditionally, therapeutic approaches have sought to modulate the pro- or anti-inflammatory limbs of inflammation, with mixed success. However, insight into the pathways by which inflammation is resolved has highlighted novel opportunities to pharmacologically manipulate these processes - a strategy that might represent a complementary (and perhaps even superior) therapeutic approach. This Review discusses the state of the art in the biology of resolution of inflammation, highlighting the opportunities and challenges for translational research in this field.
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                Author and article information

                Contributors
                uatheone@dongguk.edu
                Journal
                Arch Pharm Res
                Arch Pharm Res
                Archives of Pharmacal Research
                Pharmaceutical Society of Korea (Seoul )
                0253-6269
                1976-3786
                4 January 2021
                : 1-15
                Affiliations
                GRID grid.255168.d, ISNI 0000 0001 0671 5021, College of Pharmacy, , Dongguk University, ; Seoul, 100-715 Republic of Korea
                Author information
                http://orcid.org/0000-0003-2210-0793
                Article
                1299
                10.1007/s12272-020-01299-y
                7781431
                ccf3e8eb-424d-4d21-b644-fbc06aa8af6c
                © The Pharmaceutical Society of Korea 2021

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                : 28 October 2020
                : 23 November 2020
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100003725, National Research Foundation of Korea;
                Award ID: NRF 2018R1E1A2A02057995
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100003725, National Research Foundation of Korea;
                Award ID: NRF-2018R1A5A 2023127
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100003725, National Research Foundation of Korea;
                Award ID: NRF-2020R1A2C3004973
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100003725, National Research Foundation of Korea;
                Award ID: NRF-2020M3E5E2038356
                Award Recipient :
                Categories
                Review

                virus infection,specialized pro-resolving lipid mediators,chemerin receptor 1,fpr2/alx, sars-cov2,cytokine storm

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