Table 1.
Prospective alternative and cofactorial receptors for ACE2 SARS-CoV-2.
| Receptor [Ref] | Expression on Cells | Receptor Functions |
|---|---|---|
| ACE2 [83,84] | Epithelial cells, macrophages, platelets, endothelial cells, smooth muscle cells, many other cells. |
Main receptor for SARS-CoV-1 and SARS-CoV-2; neutralization of Ang II; formation of anti-inflammatory 1-7 Ang. |
| Chondroitin sulfate [55,79] |
Most of the cells. | Component of the cell glycocalyx; coreceptor for SARS-CoV-2 and several other viruses. |
| Neuropilin 1 (NRP1, CD304) [85,86,87] | Nerve cells of the brain and nasal cavity, endothelial cells. |
Coreceptor for binding SARS-CoV-2; coreceptor for many growth factors. The receptor function of NRP-1 depends on the cleavage of S-protein by furin. |
| AXL [88] | Expression of AXL > ACE2 in many tissues, and in the lungs and bronchi. | A putative alternative receptor for SARS-CoV-2; binds several growth factors and phosphatidylserine. |
| CD147 (Basigin) [89,90] | It is widely expressed in human tissues, highly expressed on cells of the immune system. |
The coreceptor and activator of ACE2 expression; receptor for many other viruses; polyfunctional membrane chaperone that binds and is activated by cyclophelin A and B. |
| GRP78 (BiP, HSPA5) [91,92,93,94,95] | On different cells. | Coreceptor for SARS-CoV-2; an inducible HSP of the HSP70 family; a cellular stress factor; a gateway for many viruses. |
| SR-B1 [35] | Proliferating cells, hepatocytes, macrophages, adrenal cells. |
Coreceptor for SARS-CoV-2; the main receptor for the hepatitis C virus, the HDL receptor; SR. |
| SR-H2 (Stabilin-2) [96] | Macrophages, endothelial cells. | SR; a lectin; could potentially be involved in the uptake of SARS-CoV-2 by macrophages. |
| CD209L (L-SIGN) [97,98,99] | Endothelial cells, alveolar epithelium. | An independent receptor and a cofactor for ACE2 in SARS-CoV-2 infection; cell adhesion factor. |
| CD209 (DC-SIGN) [97,98,100] | Macrophages (including alveolar), dendritic cells. | SR and alternative receptor for SARS-CoV-2; Binding of various PAMPs, including SARS-CoV-1/2 and other viruses, cell adhesion. |
| SR-E2 (Dectin-1, CD369) [100] | Macrophages, monocytes, dendritic cells, neutrophils, eosinophils. | SR, binds PAMP (β-1,3 and β-1,6 glycans). Can recognize glycans on the SARS-CoV-2 S protein and integrate with TLR2 and TLR4. |
| SR-E3 (CD206, Mannose receptor 1) [100] |
Macrophages, monocytes, dendritic cells. | SR, can bind mannose-rich microbial glycans, SARS-CoV-2 S1 protein and integrate with TLR2 and TLR4. |
| DPP4, (CD26) [101,102] | It is widely expressed on the surface of many cell types, including the respiratory epithelium. | The main receptor for MERS-CoV, a possible alternative receptor for SARS-CoV-2; a multifunctional receptor. |
| ANPE [63,103]. | Various epithelial cells, neutrophils. | A putative alternative receptor and ACE2 coreceptor for SARS-CoV-2; a well-known receptor for the entry of many CoVs. |
| ENPEP (CD249) [63,104]. | The expression pattern is similar to that of ACE2. | A putative alternative receptor and ACE2 coreceptor for SARS-CoV-2. Participates in the regulation of vascular tone. |
| ASGr1 [105] | Hepatocytes. | Receptor for many viruses, including hepatitis B virus; a possible alternative receptor for SARS-CoV-2. |
| KIM-1/TIM-1 [106] | Epithelium of the lungs and kidneys. | Probably an alternative ACE2 receptor for SARS-CoV-2. |
Ang—angiotensin; ANPE—alanylaminopeptidase; AXL—tyrosine-protein kinase receptor UFO; DPP4—dipeptidyl peptidase 4; ASGr—asialoglycoprotein receptor 1; ENPEP—CD249, Glutamylaminopeptidase; HDL—high-density lipoprotein; HSP—heat shock protein; KIM-1/TIM-1—kidney injury molecule-1/T cell immunoglobulin mucin domain 1; PAMP—pathogen-associated molecular patterns; SR-E3—CD206, Mannose receptor 1; SR—scavenger receptors; ACE2—angiotensin-converting enzyme 2.