Targeting complement cascade: an alternative strategy for COVID-19

Journal article


Ram Kumar Pandian, Sureshbabu, Arunachalam, Sankarganesh, Deepak, Venkataraman, Kunjiappan, Selvaraj and Sundar, Krishnan 2020. Targeting complement cascade: an alternative strategy for COVID-19. 3 Biotech. 10 (11). https://doi.org/10.1007/s13205-020-02464-2
AuthorsRam Kumar Pandian, Sureshbabu, Arunachalam, Sankarganesh, Deepak, Venkataraman, Kunjiappan, Selvaraj and Sundar, Krishnan
Abstract

The complement system is a stakeholder of the innate and adaptive immune system and has evolved as a crucial player of defense with multifaceted biological effects. Activation of three complement pathways leads to consecutive enzyme reactions resulting in complement components (C3 and C5), activation of mast cells and neutrophils by anaphylatoxins (C3a and C5a), the formation of membrane attack complex (MAC) and end up with opsonization. However, the dysregulation of complement cascade leads to unsolicited cytokine storm, inflammation, deterioration of alveolar lining cells, culminating in acquired respiratory destructive syndrome (ARDS). Similar pathogenesis is observed with the middle east respiratory syndrome (MERS), severe acquired respiratory syndrome (SARS), and SARS-CoV-2. Activation of the lectin pathway via mannose-binding lectin associated serine protease 2 (MASP2) is witnessed under discrete viral infections including COVID-19. Consequently, the spontaneous activation and deposits of complement components were traced in animal models and autopsy of COVID-19 patients. Pre-clinical and clinical studies evidence that the inhibition of complement components results in reduced complement deposits on target and non-target tissues, and aid in recovery from the pathological conditions of ARDS. Complement inhibitors (monoclonal antibody, protein, peptide, small molecules, etc.) exhibit great promise in blocking the activity of complement components and its downstream effects under various pathological conditions including SARS-CoV. Therefore, we hypothesize that targeting the potential complement inhibitors and complement cascade to counteract lung inflammation would be a better strategy to treat COVID-19.

KeywordsBiotechnology; Agricultural and Biological Sciences (miscellaneous); Environmental Science (miscellaneous); COVID-19, SARS-CoV-2, Complement cascade, C5a
Year2020
Journal3 Biotech
Journal citation10 (11)
PublisherSpringer Science and Business Media LLC
ISSN2190-572X
2190-5738
Digital Object Identifier (DOI)https://doi.org/10.1007/s13205-020-02464-2
Web address (URL)http://hdl.handle.net/10545/625347
http://www.springer.com/tdm
http://creativecommons.org/licenses/by-nd/4.0/
hdl:10545/625347
Publication dates19 Oct 2020
Publication process dates
Deposited06 Nov 2020, 11:41
Accepted03 Oct 2020
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Attribution-NoDerivatives 4.0 International

ContributorsKalasalingam Academy of Research and Education, Krishnankoil, Tamilnadu, India and University of Derby
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