TOKU-E Supporting COVID-19 Research
As a global manufacturer of antimicrobials, we are here to help with your COVID-19 research efforts. We are committed to providing researchers and manufacturers with the necessary antimicrobial agents used in SARS-CoV-2 research and vaccine development.
ReadyMade™ solutions
If you are involved with screening compounds for potential utility against microbial pathogens such as SARS-CoV-2, our ReadyMade Solutions are convenient, sterile, and ready to use in cell-based assays when uniformity and reliability are essential.
Nisin ReadyMade™ Solution (N084) is a natural antibacterial peptide. Antimicrobial peptides (AMP) are promising alternatives in the fight against pathogens causing human and animal infections. Small peptides can disrupt protein-protein interactions and since they have reduced immunogenicity, they are ideal candidates for novel therapeutics. Research using in-silico modeling has found that Nisin can interact with the SARS-CoV-2 spike protein receptor angiotensin-converting enzyme 2 (hACE2).
Cyclosporin A ReadyMade™ Solution (C285) is a natural oligopeptide being studied for utility against SARS-CoV-2. It has shown to inhibit SARS-CoV replication at very low concentrations, and can inhibit the replication of other coronaviruses. Since the SARS-CoV resembles the genome of SARS-CoV-2 the compound has potential utility against COVID-19.
Anisomycin ReadyMade™ Solution (A226) is a natural alkaloid anti-protozoal pyrrolidine antibiotic. Anisomycin may block the SARS-CoV-2 infection, and it can block the macrophage inflammation which may further inhibit the cytokine storm in COVID-19 disease.
Bleomycin ReadyMade™ Solution (B096) is a glycopeptide. Recently, mesenchymal stem cell secretome has been used as a strategy for COVID-19. Evidence from murine models indicate that the secretome can be used for pulmonary injuries induced with Bleomycin, due to its content: growth factors, extracellular vesicles, and exosomes. The secretome testing and production in xenofree conditions could be used as an alternative approach for SARS-Cov-2 in vivo (Deffune et al, 2020).
Co-trimoxazole (Syn: Trimethoprim-Sulfamethoxazole)(C287) belongs to the sulfonamide class and is bactericidal and antiparasitic in nature, useful against bacteria causing respiratory tract infections It also has immunomodulatory and anti-inflammatory properties and may be studied to ameliorate the cytokine storm syndrome associated with severe COVID-19 disease.
Virus propagation in cell culture
Antibiotics used in virology research protect the virus from infection by bacteria and fungi without interfering in its growth. Examples include Gentamicin Sulfate (G007), Kanamycin Sulfate (K007), Amphotericin B (A008) and MycoRid™ (M093).
Viral transport medium
Viral transport media (VTM) is critical in order to preserve the integrity of viral samples. Without preservation, the samples can degrade or become contaminated. The Centers for Disease Control (CDC) Standard Operating Procedure (SOP) (DSR-052-04) includes the addition of Amphotericin B and Gentamicin Sulfate to VTM. Amphotericin B is used at a final concentration of 0.5 µg/ml. We offer a solubilized version of Amphotericin B (A008) for easy stock solution preparation (250 µg/mL). Gentamicin is used at a final concentration of 100 µg/ml. We offer a sterile, ready-to-use solution of Gentamicin (50 mg/ml in water) (G046).
Antiviral screening
TOKU-E has the most comprehensive list of antiviral compounds and antiparasitic compounds which may have activity against COVID-19 (See Tables below). Please contact us if you are conducting compound screening.
Cell culture
A) Antibody testing and development
Antibody production is facilitated by recombinant E. coli, and Amphotericin B and MycoRid can be used to minimize contamination during culture.
B) Research on viral attachment and propagation
Cell lines used to study SARS CoV viral attachment and propagation include Vero variants, Huh-7D 12 and Caco-2.
By using our Cell Line database, you can easily review the antibiotics used in culturing these cell lines.
Vero variants
- G418 (G001)
Huh-7D
Caco-2
Vaccine development
TOKU-E Bacitracin, CulturePure (B014) can be used for vaccine development using tobacco cells. It can protect the cells and contribute to increased antibody yields. The advantages of a tobacco-produced vaccine are that it will not contain protein from mammalian cells which will alleviate the side effects such that it could be taken orally. Bacitracin, CulturePure is the only compound that performs in this application that is commercially available. Another useful compound is Vancomycin Sulfate (V010). It can be used Tobacco and sf9 (insect cells) which would also be safe for vaccine production. Kanamycin Sulfate (K008) and Gentamicin (G007) are also used in growth of CHO and Sf9 cell lines.
Re-purposing compounds for Coronavirus
A case for Colchicine
COVID-19 management strategies continues to evolve. The current mechanisms suggest that the virus role is of exaggerated activation of the innate immune system. Colchicine is one of the oldest anti-inflammatory therapeutics. The compound is FDA approved, easily administered, safe, well tolerated, inexpensive, and could reduce the risk of hospitalization and mortality.
An anti-inflammatory agent with limited immunosuppressive potential such as Colchicine (C093) could prove useful in preventing severe inflammatory injury. It may prevent the progression from inflammatory activation (phase 2) to a hyperinflammatory state (phase 3) thus its benefit is suggested to be maximized when used early, within a few days of diagnosis.
Given the large body of data demonstrating Colchicine’s inhibitory effects on neutrophil activity, cytokine generation, and the inflammation/thrombosis interface, and a lack of evidence for systemic imunosuppression, there is a rationale to study Colchicine as a potential treatment for COVID-19 (Reyes et al, 2020).
Colchicine was used in a the ColCorona trial, a phase 3, randomized, double-blind, placebo-controlled multicenter clinical study to evaluate the efficacy and safety of Colchicine in adult patients diagnosed with COVID-19 infection with at least one high-risk criterion, who are not currently hospitalized, was done with 4506 participants in Canada. The trial and was undertaken by Dr. Jean-Claude Tardif at the Montreal Heart Institute. It was funded by governments and philanthropies. The patients were given 0.5 mg of Colchicine twice daily for 3 days followed by a once-a-day dose for 27 days. The conclusion was that the rate of hospitalization or death was 21% lower among patients who received the compound. The study was clinically persuasive, and results are intended to be published in a peer-reviewed journal.
Artemisinin
Artemisinin-Piperaquine (AP) was used in a small clinical trial in China in patients with mild-to-moderate COVID-19, and results showed that the time to reach undetectable SARS-CoV-2 was significantly shorter in the AP group than in the control group. The study found that AP shortened the time the virus remained in the body. The mechanisms of how AP is improving the health of patients with COVID-19 is still being investigated.
References
Centers for Disease Control and Prevention. 2020. DSR-052-02: Preparation of viral transport medium.
ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000 Feb 29 . Identifier NCT04322682, Colchicine Coronavirus SARS-CoV2 Trial (COLCORONA) (COVID-19); 2020 March 26 [cited 2021 Jan 26][~ 6 pages]. Available from: https://clinicaltrials.gov/ct2/show/NCT04322682
Gao J, Tian Z, Yang X (2020) Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies. Biosci. Trends doi 10.5582. ePub PMID 32074550
Hoffmann M (2020) SARS-CoV-2 Cell entry depends on ACE2 and TMPRSS2 and Is blocked by a clinically proven protease inhibitor. Cell. Doi 10.1016. in press.
Letko M et al (2020) Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacoronaviruses. Nat. Microbiol. 5:562-569
Li G et al (2021) Safety and efficacy of Artemisinin-Piperaquine for treatment of COVID-19: An open-label, non-randomised and controlled trial. Int. J. Antimicrob. Agents57(1):106216
Reyes AZ et al (2020) Anti-inflammatory therapy for COVID-19 infection: The case for Colchicine. Annal. Rhematic. Dis. doi: 10.1136/annrheumdis-2020-219174 Link
Savarino A, Boelaert JR, Cassone A, Majori G and Cauda R (2003) Effects of Chloroquine on viral infections: An old drug against today's diseases? Lancet Infect. Dis. 3(11):722-727 PMID 14592603
Smith KP et al (2020) Large-scale, in-house production of viral transport media to support SARS-CoV-2 PCR testing in a multihospital health care network during the COVID-19 pandemic. J. Clin. Microbiol. 58(8):e00913-20 PMID 32404481
Takeyama N, Kiyono H and Yuki Y (2015) Plant-based vaccines for animals and humans: Recent advances in technology and clinical trials. Ther. Adv. Vaccines 3(5-6):139–154
Vaughn JL, Goodwin RH, Tompkins GJ, McCawley P (1977) The establishment of two cell lines from the insect Spodoptera frugiperda (Lepidoptera; Noctuidae). In Vitro. 13 (4): 213–217 PMID 68913
Antiviral compounds
|
Item # |
Antiviral Compound |
CAS Number |
|
A102 |
||
Antiparasitic compounds
|
Item # |
Antiviral Compound |
CAS Number |
|
P127 |
Pyrantel citrate salt |
5685-86-9 |
|
P129 |
||
|
Q011 |
Quinine hydrochloride dihydrate |
6119-47-7 |