Targeting complement cascade: an alternative strategy for COVID-19
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Targeting complement cascade: an alternative strategy for COVID‑19 Sureshbabu Ram Kumar Pandian1 · Sankarganesh Arunachalam1 · Venkataraman Deepak1,2 · Selvaraj Kunjiappan1 · Krishnan Sundar1 Received: 21 May 2020 / Accepted: 3 October 2020 © King Abdulaziz City for Science and Technology 2020
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 COVID19. 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. Keywords SARS-CoV-2 · ARDS · Inflammation · MASP2 · Complement cascade · Complement inhibitors
Introduction Innate immunity plays a critical role against various invading pathogens, in that, antigen-presenting cells, physical barriers, complement components, coagulation cascade, and immunoglobulins synergistically regulate opsonization, inflammation, and phagocytosis (Maloney et al. 2020). Innate immunity is massive and erstwhile it is puzzling to decide where the system ends, and the rest of the coordination begins (Beutler 2004). A gridded network is maintained by these immune components to preserve homeostasis and * Sureshbabu Ram Kumar Pandian [email protected] 1
Department of Biotechnology, School of Bio and Chemical Engineering, Kalasalingam Academy of Research and Education, Krishnankoil, Tamilnadu 626126, India
Department of Human Sciences, University of Derby, London, United Kingdom
2
to evade unsought immune response (Maloney et al. 2020). Although the innate immune syst
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