SARS–CoV-2 Immuno-Pathogenesis and Potential for Diverse Vaccines and Therapies: Opportunities and Challenges

Abstract

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is a novel coronavirus that emerged from Wuhan, China in late 2019 causing coronavirus disease-19 (COVID-19). SARS-CoV-2 infection begins by attaching to angiotensin-converting enzyme 2 receptor (ACE2) via the spike glycoprotein, followed by cleavage by TMPRSS2, revealing the viral fusion domain. Other presumptive receptors for SARS-CoV-2 attachment include CD147, neuropilin-1 (NRP1), and Myeloid C-lectin like receptor (CLR), each of which might play a role in the systemic viral spread. The pathology of SARS-CoV-2 infection ranges from asymptomatic to severe acute respiratory distress syndrome, often displaying a cytokine storm syndrome, which can be life-threatening. Despite progress made, the detailed mechanisms underlying SARS-CoV-2 interaction with the host immune system remain unclear and are an area of very active research. The process’s key players include viral non-structural proteins and open reading frame products, which have been implicated in immune antagonism. The dysregulation of the innate immune system results in reduced adaptive immune responses characterized by rapidly diminishing antibody titers. Several treatment options for COVID-19 are emerging, with immunotherapies, peptide therapies, and nucleic acid vaccines showing promise. This review discusses the advances in the immunopathology of SARS-CoV-2, vaccines and therapies under investigation to counter the effects of this virus, as well as viral variants.

SARS-CoV-2-Induced Gut Microbiome Dysbiosis: Implications for Colorectal Cancer

“…The severity of the illness varies with co-existing comorbidities, biological sex, and age [ 9 ]. The potent inflammatory effects from this virus due to their immune system subverting non-structural proteins result in systemic pathologies in the severely ill. SARS-CoV-2 infections have unknown long-term consequences in patients with comorbidities, such as cancer [ 10 ].…”

Host factors: Implications in immunopathogenesis of COVID-19

“…This glycoprotein was first detected in 1992 as an antigen associated with the activation of T cells [95] . CD147, NRP1, and myeloid CLRs have been listed as potential viral entry points as alternatives to the ACE2 receptor [96] .…”

“…As mentioned, the CD147 glycoprotein can also facilitate HIV-1 cell entry [97] , [98] . CD147 is responsible for stimulating the production of matrix metalloproteinases (MMPs) both in physiological and pathological processes like inflammation, tissue repair, and wound healing [96] . Receptors including CD147, angiotensin-converting enzyme 2 (ACE2), and TMPRSS2 fulfill key roles in the cell attachment and entry of coronaviruses.…”

“…Receptors including CD147, angiotensin-converting enzyme 2 (ACE2), and TMPRSS2 fulfill key roles in the cell attachment and entry of coronaviruses. The CD147 receptor is expressed in epithelial, fibroblasts, and brain cells [96] . The fact that the N protein of SARS-CoV-1 was found to coprecipitate with CD147 supported the hypothesis that various viral components interact through different pathways with this transmembrane protein [96] .…”

A brief molecular insight of COVID-19: epidemiology, clinical manifestation, molecular mechanism, cellular tropism and immuno-pathogenesis

“…In the past two decades, coronaviruses are responsible for the three epidemics namely COVID-19, SARS and MERS. This novel SARS-CoV-2 is a zoonotic virus, belong to Coronaviridae family of Nidovirales order [ 3 ]. This family got its name “coronavirus” because of the crown-like appearance of its spike protein.…”