Molecular Pathogenesis, Immunopathogenesis and Novel Therapeutic Strategy Against COVID-19

Abstract

The coronavirus disease 2019 (COVID-19), is a highly contagious transmittable disease caused by a recently discovered coronavirus, pathogenic SARS-CoV-2. Followed by the emergence of highly pathogenic coronaviruses in 2003 SARS-CoV, in 2012 MERS-CoV, now in 2019 pathogenic SARS-CoV-2, is associated with a global “pandemic” situation. In humans, the effects of these viruses are correlated with viral pneumonia, severe respiratory tract infections. It is believed that interaction between angiotensin converting enzyme 2 (ACE2) cell receptor and viral Spike protein mediates the coronavirus entry into human respiratory epithelial cells and establishes the host tropism. ACE2 receptor is highly expressed in airway epithelial cells. Along with viral-receptor interaction, proteolytic cleavability of S protein has been considered as the determinant of disease severity. Several studies highlight the occurrence of impaired host immune response and expression of excessive inflammatory response especially cytokines against viral infection. The mechanisms of SARS-CoV-2 induced acute lung injury are still undefined; however, the term cytokine storm has now been recognized to be closely associated with COVID-19. The levels of inflammatory mediators from cytokine storm cause damage to the host cells. In particular, the proinflammatory cytokine IL-6 appears to be the key mediator in early phase of virus-receptor interaction; however, secreted IL-6 might not be representative of lung inflammation. Understanding the cellular, and molecular factors involved in immune dysregulation and the high virulence capacity of COVID-19 will help in potential targeted therapy against it. “Drug repurposing” and “molecular docking analysis” is considered as an attractive alternative approach in analyzing suitable drug candidates to combat SARS-CoV-2 infection. Globally, extensive research is in progress to discover a new vaccine for novel COVID-19. Moreover, our review mainly focuses on the most state-of-the-art therapeutic approach mediated by “Mannose-binding lectin (MBL).” One of the most significant molecules of innate immunity is MBL. It plays a major role in the activation of the complement system as an ante-antibody prior to the response of any particular antibody. Recombinant human MBL can be used as immunomodulators against SARS-CoV-2.

COVID-19: An overview and a clinical update

“…SARS-CoV-2 infection development mainly varies upon the interaction between the virus and the individual's immune system. On the other hand, viral factors like the type of virus, virus viability, mutation potential, and the individual immune system elements like gender, age, genetics, and nutritional status contribute to the severity of the diseases[ 51 ].…”

A double edged-sword - The Complement System during SARS-CoV-2 infection

“…Although the precise mechanisms underlying the acute lung injury induced during SARS-CoV-2 infection are still undefined, inflammatory mediators of the cytokine storm have been recognized to cause damage to the host cells [ 75 ]. The term cytokine storm has been used to refer to dysregulation of the immune system, with a substantial release of pro-inflammatory cytokines (mainly IL-6, IL-1, TNF-α and interferon) by several immune cells, such as macrophages, dendritic cells, natural killer cells, T and B lymphocytes [ 76 ].…”

The Influence of the Lectin Pathway of Complement Activation on Infections of the Respiratory System

“…Data reported by Magro et al (112) evidenced depositions of MASP-2, co-localized with C4d and SARS-CoV-2 spike glycoprotein (S-gp) in septal capillaries and interalveolar septa of the lungs from COVID-19 non-survivors. Recently, recombinant MBL has been mooted as a therapeutic agent, acting via inhibition of binding of S-gp to the angiotensin converting enzyme 2 (ACE2) cell receptor and by promoting phagocytosis (113).…”