Table 2.
Potential therapeutic targets associated with coronavirus infections in humans.
| Target | Function | Coronavirus type | Reference |
|---|---|---|---|
| Angiotensin-converting enzyme 2 (ACE2) | Functional cellular receptor for SARS-CoV and SARS-CoV-2 (COVID-19)* | SARS-CoV SARS-CoV-2 |
(Yan et al., 2020) |
| Spike glycoprotein (S protein)—during viral infection in cleaved into S1 and S2 subunits | Mediates receptor recognition and membrane fusion for viral entry. S1 subunit: contains receptor-binding domain (RBD)** which binds to the peptidase domain (PD) of ACE2 S2 subunit: responsible for membrane fusion; cleaved by host proteases once S1 binds to ACE2 which is needed for a viral infection to occur |
SARS-CoV | (Gallagher and Buchmeier, 2001) |
| Cathepsin L–cysteine peptidase | Facilitates the cleavage of the S protein of SARS-CoV, therefore aids in the activation of membrane fusion | SARS-CoV | (Simmons et al., 2005) |
| Transmembrane protease serine 2 (TMPRSS2) | Cleaves C-terminal segment of ACE2, enhancing S-protein viral infection | SARS-CoV | (Shulla et al., 2011) |
| Nonstructural protein 1 (Nsp1) coronavirus virulence factor | Induces host mRNA degradation by interacting with the hosts 40S ribosomal subunit and inhibits type-I interferon production | SARS-CoV | (Kamitani et al., 2006; Narayanan et al., 2008) |
| Open reading frame 7a (ORF7a) coronavirus virulence factor | ORF7a binds directly to bone marrow stromal antigen 2 (BST-2), blocking the activity of BST-2 by disrupting the glycosylation of BST-2. BST-2 mediates the restriction of virus-like particle release | SARS-CoV | (Taylor et al., 2015) |
| Replicase polyproteins | Involved in the transcription and replication of viral RNAs. Encoded by open reading frames (ORF) 1a and 1b. | SARS-CoV | (Wu et al., 2020) |
| Papain-like proteinase (PLpro) | Essential in the replication and infection for coronaviruses. Cleaves the N-terminal of the replicase polyprotein causing the release of Nsp1, Nsp2 and Nsp3, which are in turn involved in viral replication | SARS-CoV | (Harcourt et al., 2004) |
| Viral main protease (3CLpro, also called Mpro) –cysteine protease | Controls the activities of the coronavirus replication complex and is therefore essential for viral replication*** | SARS-CoV SARS-CoV-2 |
(Anand et al., 2003) |
| RNA dependent RNA polymerase (RdRp) (nsp12) | Essential protease enzyme that catalyzes the replication of RNA from the RNA template | SARS-CoV SARS CoV-2 |
(Lung et al., 2020) |
| Non-structural protein 13 (NSP13)/helicase | Enhances the efficiency of viral replication and proliferation through its NTPase, duplex RNA/DNA-unwinding and RNA-capping activities | SARS CoV | (Shum and Tanner, 2008) |
*Functional cellular receptor (ACE2) are identical for SARS-CoV and SARS-CoV-2 (Ou et al., 2020); **Homology of the spike-receptor binding domain (RBD) sequence between SARS-CoV-2 and SARS-CoV is 76% (Wu et al., 2020); ***The SARS-CoV-2 main protease is closely related (96% identity) to the SARS-CoV protease (Chen and Du, 2020).