Coronavirus Antivirals

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.

Products
Background
Literature (1)
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
6358 Atovaquone
Exhibits anti-MERS-CoV activity in vitro; DHODH inhibitor
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
Identified as targeting human host proteins that interact with SARS-CoV-2
7189 Saracatinib
Inhibits MERS-CoV, other coronaviruses and dengue virus
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).

Immunofluorescence assay using Rabbit Anti-SARS-CoV Nucleocapsid Antibody (#NBP2-44205 - part of SARS Nucleocapsid Protein Antibody Pack #NBP3-05695), showing viral protein synthesis

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 Antivirals

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

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.

Compound Repurposing

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.

Literature for Coronavirus Antivirals

Tocris offers the following scientific literature for Coronavirus Antivirals to showcase our products. We invite you to request* your copy today!

*Please note that Tocris will only send literature to established scientific business / institute addresses.


New Product Guide

New Product Guide [Spring/Summer 2019]

Our new product guide highlights over 215 new products added to the Tocris Bioscience range during the first half of 2019.

  • 7-TM Receptors
  • Enzymes
  • Enzyme-Linked Receptors
  • Ion Channels
  • Nuclear Receptors
  • Transporters
  • Chemogenetics
  • Epigenetics
  • Fluorescent Imaging
  • PROTACs
  • Signal Transduction
  • Stem Cells