Using Existing Therapeutics Against SARS-CoV-2
Currently, there are no approved drugs to treat the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection that causes coronavirus disease 2019 (COVID-19). Existing FDA-approved drugs that have a known favorable safety profile are being examined for strategies to treat the disease and fast-track a treatment plan.
Tools to Study SARS-CoV-2-Host Interactions
|Cat. No.||Product Name|
ACE2 (human) Monoclonal Antibody (Clone AC18F)
ACE2 (human) Monoclonal Antibody – Biotinylated (Clone AC18F)
ACE2 (human) Monoclonal Antibody (Clone AC384)
SARS-CoV-2 Spike and Nucleocapsid Proteins
|Cat. No.||Product Name|
SARS-CoV-2 Surface Glycoprotein (433-506)
SARS-CoV-2 Surface Glycoprotein Receptor Binding Motif
SARS-CoV-2 Surface Glycoprotein Receptor Binding Domain
SARS-CoV-2 Nucleocapsid Protein
qRT-PCR Detection Assays
|Cat. No.||Product Name|
SARS-CoV-2 qPCR detection 1-plex assay-ORF1ab
SARS-CoV-2 qPCR detection 1-plex assay-N
SARS-CoV-2 qPCR detection 1-plex assay-RdRP
SARS-CoV-2 qPCR detection 1-plex assay-E
NEW SARS-CoV-2 Spike-ACE2 Interaction Inhibitor Screening Assay Kit
Cayman’s SARS-CoV-2 Spike-ACE2 Interaction Inhibitor Screening Assay Kit provides a robust and easy-to-use platform for identifying novel inhibitors of the SARS-CoV-2 spike and ACE2 interaction. The assay uses a recombinant rabbit Fc-tagged SARS-CoV-2 spike S1 RBD that binds to a plate precoated with a mouse anti-rabbit antibody. A recombinant His-tagged ACE2 protein binds the spike RBD and the complex is detected with an HRP-conjugated anti-His antibody. This assay includes a control for competition of the SARS-CoV-2 spike RBD-ACE2 interaction.
Cat No. 502050
Cayman Currents Issue 33: Antiviral Strategies for Emerging Infectious Diseases
Virus-Host Fusion Inhibitors
The broad-spectrum antiviral arbidol blocks viral fusion with target membranes, prohibiting viral entry into cells. Because it targets a common critical step for viral replication, it is effective against numerous viruses, including influenza A, B, and C as well as hepatitis B and C. 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 inhibiting the Abl kinase pathway is also a promising target for the development of antiviral therapies, since this kinase activity is required for entry of coronaviruses. Abl kinases are composed of distinct domains that enable them to act as scaffolds for signaling complexes and to regulate protein function through phosphorylation of downstream targets. Cayman offers several Abl kinase inhibitors that can be used to study the coronavirus membrane fusion step.
In addition to the coronavirus entering the host by binding to the host cell’s ACE2 receptor, participation of ACE in the renin-angiotensin system has been implicated in the acute, accelerated lung fibrosis associated with coronavirus infection. ACE inhibitors may further play a role in disallowing viral fusion of the coronavirus to the host cell and entry into the cell, denying its pathway to replication.
In addition to spike protein binding of the ACE2 receptor, viral entry requires spike protein priming by host cellular proteases. This involves spike protein cleavage at S1/S2 surface units and the S2’ site and allows fusion of viral and cellular membranes. This activity is essential for viral spread and pathogenesis in the infected host. This is evidenced by the ability of the serine protease inhibitor camostat (mesylate), which is active against TMPRSS2 to partially block SARS-CoV-2-spike protein-driven entry into cells. When camostat (mesylate) was combined with E-64d, an inhibitor of cathepsin B and L, full inhibition was achieved.
|HCV Protease Inhibitors||HIV Protease Inhibitors||Influenza Neuraminidase Inhibitors|
|Boceprevir||Indinavir (sulfate)||Oseltamivir (Phosphate)|
|Simeprevir (sodium salt)||Nelfinavir (mesylate)|
RNA-Dependent RNA Polymerase Inhibitors
Once inside the host cytoplasm, the single-stranded RNA virus serves as an RNA template that is replicated into complementary strands through the action of the RNA-dependent RNA polymerase (RdRP). The initiation step of RNA synthesis involves the addition of a nucleoside triphosphate to the 3’ end.
Oxysterol-Binding Protein Inhibitors
During viral replication, oxysterol-binding protein (OSBP) plays a vital role in producing the membrane-bound viral replication organelles that form at the membrane contact sites between the endoplasmic reticulum (ER) and Golgi. Coronaviruses may also be a suitable target for OSBP-targeted compounds.
Endosomal pH Regulators
Viruses entering host cells by endocytosis require an acidic pH in endosomal vesicles for virus-host fusion and to carry out the replication process. The antimalarial agent chloroquine (phosphate) is a weak base that shows broad-spectrum antiviral activities by increasing the endosomal pH required for viral activity.
|Chloroquine (phosphate)||Hydroxychloroquine (sulfate)|
Nuclear Transport Inhibitors
Another step that is essential for viral replication is the integration of the nucleocytoplasmic shuttling of viral proteins through the action of host importin proteins.
|Ivermectin B1a||Ivermectin B1b||Δ2-Avermectin B1a|
|epi-Ivermectin B1a||2,3-Dehydro-3,4-dihydro Ivermectin|
REDOX Homeostasis Disruption
ER stress and subsequent activation of the unfolded protein response (UPR) are thought to contribute significantly to viral replication during a coronavirus infection. Indeed, cells overexpressing the SARS-CoV spike protein and other viral proteins exhibit high levels of UPR activation, and the expression of the ER protein folding chaperones GRP78, GRP94, and other ER stress-related genes is increased to maintain proper protein folding. The gold-thiol complex auranofin functions to inhibit redox enzymes, which leads to a dysregulation of redox homeostasis that induces oxidative stress and apoptosis.