Currently, there are no drugs approved to treat the disease caused by the SARS-CoV-2 coronavirus and causing the coronavirus disease 2019 (COVID-19). Existing drugs are being tested to treat the disease and speed up a treatment plan.
Cayman’s ACE2 Receptor-Spike Protein Interaction Inhibitor Detection Assay Kit provides a robust and easy-to-use platform for identifying novel inhibitors of the interaction. This assay includes a control for the compeence of the SARS-CoV-2 spike RBD-ACE2 interaction.
Cat. No. 502050
The antiviral arbidol is a broad-spectrum antiviral that blocks the fusion of viral and host membranes, prohibiting viral entry into cells. A study has revealed that arbidol can effectively inhibit SARS-CoV-2 infection at a concentration of 10-30 µM in vitro.
Blocking virus-host fusion through inhibition of the Abl kinase pathway is also a promising target for the development of antiviral therapies, as this kinase activity is necessary for coronavirus entry. Imatinib was identified as an inhibitor of SARS-CoV and MERS-CoV in a high throughput screening. Cayman Chemical offers several Abl kinase inhibitors that can be used to study the fusion step of the coronavirus membrane:
On the other hand, once the coronavirus enters the host, it binds to the ACE2 receptor of the host cell. The involvement of ACE in the renin-angiotensin system has been implicated in the acute pulmonary fibrosis that causes the COVID-19 disease. ACE inhibitors may play an additional role in disabling viral fusion of the coronavirus to the host cell and entry into the cell, inhibiting replication.
In addition to the binding of the Spike protein to the ACE2 receptor, viral entry requires preparation of the Spike protein by host cellular proteases. This involves cleavage of the Spike protein at the S1 / S2 surface units and the S2 ‘anchor site allows for the fusion of viral and cellular membranes. This activity is essential for viral spread and pathogenesis in the infected host. This hypothesis was evidenced by the ability of camostat (mesylate) which is active against TMPRSS2 to partially block the entry of SARS-CoV-2 into cells. When camostat (mesylate) was combined with E-64d, an inhibitor of cathepsin B and L, complete inhibition was achieved.
| HCV Protease Inhibitors | HIV Protease Inhibitors | Influenza Neuraminidase Inhibitors |
| Asunaprevir | Darunavir | Oseltamivir Acid |
| Boceprevir | Indinavir (sulfate) | Oseltamivir (Phosphate) |
| Grazoprevir | Lopinavir | Peramivir |
| Simeprevir (sodium salt) | Nelfinavir (mesylate) | |
| Telaprevir | Ritonavir | |
| Saquinavir (mesylate) |
Once within the host cytoplasm, the single-stranded RNA virus serves as an RNA template that replicates in complementary strands through the action of RNA-dependent RNA polymerase (RdRP). The initiation step of RNA synthesis involves the addition of a nucleoside triphosphate to the 3 ‘end.
During viral replication, oxysterol binding protein (OSBP) plays a vital role in the production of the membrane-bound viral replication organelles that form at the membrane contact sites between the endoplasmic reticulum (ER) and Golgi. For this reason, OSBP is a good candidate for a therapeutic target.
Viruses that enter host cells by endocytosis require an acidic pH in the endosomal vesicles for virus-host fusion and to carry out the replication process. The antimalarial agent cloroquina (fosfato) is a weak base that exhibits broad-spectrum antiviral activity by increasing the endosomal pH required for viral activity.
Another step that is essential for viral replication is the integration of nucleo-cytoplasmic transport of viral proteins through the action of host importin proteins.
Oxidative stress and subsequent activation of the UPR protein are believed to contribute significantly to viral replication during a coronavirus infection. In fact, cells that overexpress the Spike SARS-CoV protein and other viral proteins exhibit high levels of UPR activation, and the expression of chaperones for protein folding: GRP78, GRP94, and other ER stress-related genes are increases to maintain proper protein folding. The gold-thiol Auranofin complex works to inhibit redox enzymes, leading to deregulation of redox homeostasis that induces oxidative stress and apoptosis.
