Table 2.
Host cellular targets of various SARS-CoV, MERS-CoV and SARS-CoV-2 proteins.
| Host target proteins | SARS-CoV proteins | MERS-CoV proteins | SARS-CoV-2 proteins | Stage of viral life cycle and function | References |
|---|---|---|---|---|---|
| ACE2 | S | S | Attachment and entry Host cell receptor |
Weiss and Leibowitz, 2011; Hoffmann et al., 2020; Lan et al., 2020; Valencia et al., 2020 | |
| DPP4 | S | Attachment and entry Host cell receptor |
Li, 2015; Seys et al., 2018; Valencia et al., 2020 | ||
| IFITM | Known | Known | Not known | Entry restricted | Wrensch et al., 2014; Liao et al., 2019 |
| Cathepsin L | S | S | S | Cleavage and activation | Kleine-Weber et al., 2018; Ou et al., 2020 |
| Furin | S | S | Cleavage and activation | Coutard et al., 2020; Xia et al., 2020 | |
| TMPRSS2 | S | S | S | S protein priming | Kleine-Weber et al., 2018; Iwata-Yoshikawa et al., 2019; Hoffmann et al., 2020; Meng et al., 2020 |
| GSK3 | N | Phosphorylation Facilitation of viral replication |
Wu et al., 2009 | ||
| IFN pathway | NSP13, NSP14,NSP15 ORF6 and ORF9b | Antagonize interferon pathway | Lei et al., 2020; Sa Ribero et al., 2020 | ||
| NF-κB | N | NSP13, ORF9c | Inflammation | Liao et al., 2005; Dosch et al., 2009 | |
| E3 ubiquitin ligase: TRIM59 and MIB1 | ORF3a and NSP9, respectively | Interference with antiviral innate immunity | Kondo et al., 2012; Gil et al., 2020 | ||
| E3 ubiquitin ligase: RCHY1 | NSP3 | PLPro | Abolishing of p53 mediated antiviral activity | Ma-Lauer et al., 2016; Gordon et al., 2020 | |
| CAMK2D | NSP3 | Interference in IFN pathway | Ma-Lauer et al., 2016 | ||
| NUP98-RAE1 | ORF6 | Antagonize interferon pathway | Addetia et al., 2020; Gordon et al., 2020 | ||
| Stress granule proteins: G3BP1 and G3BP2, LARP1, CK2, UPF1, MOV10 | N | Abrogation of IFN signaling | Cascarina and Ross, 2020; Gordon et al., 2020 | ||
| Stress granule proteins | p4a interacts with dsRNA | Inhibition of stress granule formation | Rabouw et al., 2016; Nakagawa et al., 2018 | ||
| N-linked glycosylation enzymes | S and M | S | S | Facilitation of lectin-mediated virion attachment by S | Zhou et al., 2010; Watanabe et al., 2020; Zhao P. et al., 2020 |
| Caveolin | ORF3a | Might regulate virus uptake and trafficking of viral structural proteins | Padhan et al., 2007 | ||
| TRAF3 and ASC | ORF3a | Activation of NLRP3 inflammasome | Siu et al., 2019 | ||
| RUNX1b | ORF3b | Immunomodulation | Varshney et al., 2012 | ||
| KPNA2 | ORF6 | Modulation of host protein nuclear transport and IFN-1 signaling | Frieman et al., 2007 | ||
| KPNA4 (importin-α3) | p4b | Evasion of innate response | Canton et al., 2018 | ||
| Bcl-xL | ORF7a, E | Induction of apoptosis Lymphopenia |
Tan et al., 2007 | ||
| LFA-1 | ORF7a | Attachment factor on leukocytes | Hänel and Willbold, 2007 | ||
| Calcineurin/NFAT pathway | NSP1 | Induction of IL2 Immunopathogenesis |
Pfefferle et al., 2011 | ||
| PHB1 and PHB2 | NSP2 | Might be altering cell cycle progression, cellular differentiation, mitochondrial biogenesis | Cornillez-Ty et al., 2009 | ||
| dsRNA | p 4a | Sequestration of dsRNA, suppression of PKR-dependent translation, suppression of RIG-I and MDA5 | Rabouw et al., 2016 | ||
| Polyprotein-cleaving protease activity | PLPro (NSP3) | PLPro (NSP3) | PLPro (NSP3) | Deubiquitination Antagonize innate immunity | Grum-Tokars et al., 2008; Clementz et al., 2010; Fung and Liu, 2019 |
| PALS1 | E | Breaching of alveolar wall | Teoh et al., 2010 | ||
| Na+/K+ ATPase α-1 subunit and Stomatin | E | Reduction in activity of epithelial Na channel | Nieto-Torres et al., 2014; Schoeman and Fielding, 2019 | ||
| hnRNPA1 | N | Might regulate viral RNA synthesis | Shi and Lai, 2005 | ||
| Cyclophilin A | N | Interferon pathway Might be crucial for virus infection |
Yurchenko et al., 2010; Tanaka et al., 2013 |
ACE2, Angiotensin-converting enzyme; DPP4, Dipeptidyl-peptidase; IFITM, Interferon-induced transmembrane protein; GSK3, Glycogen synthase kinase; TRIM59, Tripartite motif-containing protein; MIB1, Mindbomb E3 ubiquitin protein ligase; NUP98, Nuclear pore complex protein; RAE1, Ribonucleic acid export; G3BP, Ras-GTPase-activating SH3 domain binding protein; mTOR-regulated translational repressor LARP1, La ribonucleoprotein; CK2, casein kinase; mRNA decay factors UPF1, Up-frameshift) and MOV10, Moloneyleukemia virus 10 like; NFAT, Nuclear factor of activated T-cells; IL2, Interleukin; PKR, Protein kinase R; PLPro, papain-like protease; Bcl-xL, B-cell lymphoma-extra large; PALS1, Proteins associated with Lin seven; hnRNPA1, Heterogenous nuclear ribonucleoprotein; RUNX1b, Runt-related transcription factor; KPNA2, karyopherin alpha 2; LFA-1, lymphocyte function-associated antigen 1; PHB,),TRAF3, TNF receptor-associated factor3; ASC, apoptosis-associated speck-like protein containing a caspase recruitment domain; NLRP3, NOD-,LRR-and pyrin domain-containing protein),RCHY1, ring-finger and CHY zinc finger domain-containing 1; CAMK2D, calcium/calmodulin-dependent protein kinase II delta.