Table 2 Three pathways basically implicated and associated with SARS-CoV-2 [188]
Classification | Mechanism | Signaling pathways | Viral Pathogenesis |
|---|---|---|---|
1. ACE2 and TLR pathway | 1S-protein has been proposed to have the most substantial protein‒protein interaction with TLR4 [55,56,57,58,59,60] | 2TLR2 and TLR4 are expressed intracellularly in dendritic, epithelial, and endothelial cells. TLRs in modulation of COVID-19 cytokine storm signaling in SARS-CoV-2 [50, 60,61,62,63] | Neurological symptoms induced by TLRs or S-protein [50, 59,60,61, 63]. Clinically evident or exacerbated with viral diseases or aging [64, 65] |
2. Neuropilin‑1 pathway | 3NRP1 acts as a host cell mediator that can increase SARS-CoV-2 infectivity and contribute to its tissue/organ tropism [66,67,68] | NRPs are associated with numerous signaling pathways: 4VEGF [68], 5EGF [69], 6FGF [70], 7HGF [71, 72], 8IGF [73], 9PDGF [74, 75], 10TGFβ [76], and 11DPP-4 [77] | NRP-1 functions as a coreceptor for VEGF, HGF, PDGF, EGF, FGF, IGF, TGFβ, and DPP4, functionally involved in the migration and invasion of various cells, membrane disorders, angiogenesis as a hub receptor in the vascular system [78] |
3. Spike protein pathway | The interaction of 12ACE2–TLRs with SARS-CoV-2 S-protein in human 13VSELs and 14HSCs activates the NLRP3 inflammasome [57, 62, 79,80,81] | S-protein activates the NLRP3 Inflammasome and ACE2 is expressed on very small CD45 − precursors of hematopoietic and endothelial Cells and in Response to NLRP3 inflammasome with distinct epigenetic and gene expression signatures [82] | 15PF4 dependent syndrome |