Coronaviruses are enveloped, positive-sense single-stranded RNA viruses encapsulated within a nucleocapsid having helical symmetry. The causative agents of two outbreaks of SARS (severe acute respiratory syndrome) in 2003 and 2019, as well as an outbreak of Middle East respiratory syndrome (MERS) in 2012, are members of a subgroup of coronaviruses known as betacoronaviruses. The viral genome of betacoronaviruses encodes more than 20 proteins, some of which show promise as targets for coronavirus antiviral medicines.
Cat. No. | Product Name / Activity |
---|---|
4274 | AP 24534 |
Identified as targeting human proteins in the SARS-CoV-2 interactome; potent multi-kinase and pan-Bcr-Abl inhibitor | |
7283 | Apilimod dimesylate |
Inhibits cellular entry by SARS-CoV-2, MERS-CoV and MHV S pseudovirions; potent and selective PIKfyve inhibitor | |
7235 | Arbidol |
Inhibits replication of SARS-CoV-2 in vitro; broad spectrum antiviral | |
4600 | Auranofin |
Inhibits SARS-CoV-2 infection in vitro | |
7222 | Baricitinib |
In silico modelling predicts inhibition of SARS-CoV-2 cell entry; highly potent JAK inhibitor | |
3193 | Camostat mesylate |
Inhibits entry of SARS-Cov-2 into lung cells; TMPRSS2 inhibitor | |
4109 | Chloroquine diphosphate |
Inhibits SARS-CoV-2 infection in vitro | |
6357 | Ciclesonide |
Inhibits replication of SARS-CoV-2 in vitro; glucocorticoid | |
0460 | Cinanserin hydrochloride |
Inhibits replication of SARS-CoV; Mpro inhibitor and 5-HT2 antagonist | |
0970 | Cycloheximide |
Exhibits anti-MERS-CoV activity in vitro; protein synthesis inhibitor | |
1101 | Cyclosporin A |
Inhibits coronavirus replication; cyclophilin inhibitor | |
7223 | Dabrafenib mesylate |
Targets human proteins in the SARS-CoV-2 interactome; potent and selective B-Raf, CDK16 and NEK9 inhibitor | |
1467 | Daunorubicin hydrochloride |
Identified as targeting human proteins in the SARS-CoV-2 interactome; DNA topoisomerase II inhibitor | |
4583 | Digoxin |
Exhibits anti-MERS-CoV activity in vitro; Na+/K+ ATPase inhibitor | |
3807 | Disulfiram |
SARS-CoV-2 Mpro inhibitor; also reversibly stimulates SERCA Ca2+-ATPase | |
4545 | E 64d |
Inhibts entry of SARS-CoV-2 into lung cells in combination with Camostat (Cat. No. 3193); cathepsin inhibitor | |
6986 | EG 00229 trifluoroacetate |
Inhibits binding of cleaved spike protein of SARS-CoV-2 to neuropilin 1 (NRP1); neuropilin 1 antagonist | |
3631 | FK 506 |
Identified as targeting human proteins in the SARS-CoV-2 interactome; potent calcineurin inhibitor | |
3259 | Gemcitabine hydrochloride |
Inhibits replication of coronaviruses; DNA synthesis inhibitor | |
7280 | GRL 0617 |
Coronavirus PLpro inhibitor | |
7227 | GS 441524 |
Displays antiviral activity against MERS-CoV, SARS-CoV and SARS-CoV-2; viral RNA-dependent RNA polymerase (RdRp) inhibitor; active metabolite of Remdesivir (Cat. No. 7226) | |
1416 | Homoharringtonine |
Inhibits SARS-CoV-2 infection in vitro; inhibits protein synthesis | |
5648 | Hydroxychloroquine sulfate |
Inhibits SARS-CoV-2 viral infection in vitro | |
1708 | Indomethacin |
Identified as targeting human proteins in the SARS-CoV-2 interactome | |
1260 | Ivermectin |
Inhibits replication of SARS-Cov-2 in vitro; antiparasitic and antiviral | |
2959 | Lercanidipine hydrochloride |
Exhibits anti-MERS-CoV activity in vitro; CaV1.x blocker | |
3765 | Linezolid |
Identified as targeting human proteins in the SARS-CoV-2 interactome; antibiotic | |
0840 | Loperamide hydrochloride |
Inhibits replication of coronaviruses in vitro; peripherally acting μ opioid agonist and Ca2+ channel blocker | |
7052 | Lopinavir |
Inhibits SARS-CoV-2 replication in vitro; highly potent and selective HIV-1 protease inhibitor | |
6819 | Mefloquine hydrochloride |
Exhibits antiviral activities against SARS-CoV-2; also Cx36 and Cx50 gap channel blocker | |
2864 | Metformin hydrochloride |
Identified as targeting human proteins in the SARS-CoV-2 interactome; antidiabetic | |
7230 | MPro N3 |
Coronavirus Mpro inhibitor | |
3766 | Nelfinavir mesylate |
Exhibits anti-MERS-CoV activity in vitro; potent HIV-1 protease inhibitor | |
2583 | Omeprazole |
Enhances anti-SARS-CoV-2 activity of serine protease inhibitors | |
1076 | Ouabain |
Exhibits anti-MERS-CoV activity in vitro; Na+/K+ ATPase inhibitor | |
1125 | Quercetin |
Inhibits SARS-CoV Mpro; also non-selective PI 3-kinase inhibitor | |
1292 | Rapamycin |
Inhibits MERS-CoV infection; mTOR inhibitor and immunosuppressant | |
7226 | Remdesivir |
Displays antiviral activity against MERS-CoV, SARS-CoV and SARS-CoV-2; viral RNA-dependent RNA polymerase (RdRp) inhibitor | |
4501 | Ribavirin |
Inhibits cytopathic effect of SARS-CoV in vitro; guanosine analog and IMPDH inhibitor | |
7064 | Ruxolitinib |
Targets human proteins in the SARS-CoV-2 interactome; potent and selective JAK1/JAK2 inhibitor | |
7191 | Santacruzamate A New |
Identified as targeting human host proteins that interact with SARS-CoV-2 | |
7189 | Saracatinib |
Inhibits MERS-CoV, other coronaviruses and dengue virus | |
7192 | SMIP 004 New |
S-phase kinase-associated protein 2 (SKP2) inhibitor; inhibits MERS-CoV replication and induces autophagy in infected cells | |
1138 | Thapsigargin |
Inhibits SARS-CoV-2 infection in vitro; SERCA inhibitor | |
2815 | Valproic acid, sodium salt |
Identified as targeting human proteins in the SARS-CoV-2 interactome; HDAC inhibitor | |
0654 | Verapamil hydrochloride |
Targets human proteins in the SARS-CoV-2 interactome; CaV1.x blocker |
Coronaviruses are spherical viruses with a large genome (approximately 27 to 32 kb) enclosed in a lipid bilayer with surface glycoprotein projections that give the virus the appearance of having a crown, hence the name coronavirus. There are four types of coronavirus: Alphacoronaviruses and Betacoronaviruses infect only mammals, while Gammacoronavirus and Deltacoronavirus infect birds. In humans coronaviruses cause respiratory tract infections with symptoms ranging from mild, similar to the common cold, to severe pneumonia-like symptoms, as seen with SARS (severe acute respiratory syndrome), MERS (Middle East respiratory syndrome) and COVID-19. They are also responsible for a number of economically important animal diseases, including avian infectious bronchitis virus (IBV) and porcine transmissible gastroenteritis virus (TGEV).
Figure 1: Immunofluorescence assay using Rabbit Anti-SARS-CoV Nucleocapsid (N) Antibody (#NBP2-44205 - part of SARS Nucleocapsid Protein Antibody Pack #NBP3-05695), showing viral protein synthesis. VeroE6 cells were infected with rSARS-CoV-2. Mock: non-infected cells. At 48 hpi cells were fixed and prepared for immunofluorescence staining with primary antibodies directed against double-stranded RNA (dsRNA) [green] and SARS-CoV Nucleocapsid (N) [red]. Nuclear Counterstain (DAPI, Cat. No. 5748) [blue].
SARS-CoV-2 is a coronavirus responsible for the outbreak of COVID-19, a form of severe acute respiratory syndrome (SARS) that emerged in the city of Wuhan, China, in 2019. SARS-CoV-2 enters the lower respiratory system causing viral pneumonia; it may also affect the gastrointestinal system, heart, kidney, liver, and central nervous system leading to multiple organ failure.
Several SARS-CoV-2 viral proteins are being investigated as potential therapeutic targets. The spike (S) protein, a structural protein on the outside of the nucleocapsid of coronaviruses, is one such protein, which has potential as a target for coronavirus antiviral medicines. The virus is able to enter the host cell by binding of the S protein to the host protease angiotensin converting enzyme 2 (ACE2) on the cell surface. The host protein ACE2, which acts as a receptor for SARS-CoV-2, is also a possible target for antiviral therapies. ACE2 is highly expressed in lung alveolar cells and high expression levels are also seen in glandular cells, endothelial cells, and enterocytes in the gastrointestinal system. Another host protein, the protease TMPRSS2 is also essential for host cell invasion, by activating the S protein and enhancing cell entry by SARS-CoV-2. The SARS-CoV-2 S-protein is also thought to be cleaved by the endoprotease furin.
Two viral proteases, SARS coronavirus main proteinase (Mpro also known as 3C-like protease or 3CLpro) and papain-like protease, (PLpro) both of which are essential for virus replication, are also being investigated as potential antiviral targets. These proteases cleave the two translated polyproteins, PP1A and PP1AB, into functional proteins. SARS-CoV and SARS-CoV-2 3CLpro gene sequences have approximately 96% homology.
MERS is another severe respiratory infection caused by MERS-CoV that emerged in the Middle East region in 2012. MERS-CoV was originally thought to have been transmitted from camels, although more recently it has been suggested that it originated in bats. Unlike SARS-CoV-2, MERS-CoV uses dipeptidyl peptidase 4 (DPP4) as a receptor to infect lung cells, which could be a target for antivirals to treat this infection.
Repurposing existing therapies is an approach being widely investigated to discover treatments for COVID-19. Screening compound libraries, such as the Tocriscreen library of FDA approved drugs (Cat. No. 7200), for their activity against known viral or host targets could aid the rapid discovery of products that can prevent/treat the infection or alleviate symptoms in patients.