Mizoribine for the Treatment of SARS-CoV-2

Given the severity of 2019-nCoV infection, it is desirable to be ready for control of this disease, even after this outbreak has ended. Nucleoside analogs represent the largest class of small molecule-based antivirals, which currently form the backbone of chemotherapy of infections caused by diverse viruses. Creative Biolabs is a well-recognized leader in the field of antiviral drug discovery. Equipped with world-leading technology platforms and professional scientific staff, Creative Biolabs is pleased to offer imidazole nucleoside mizoribine and its validation service for the treatment of 2019-nCoV. We are confident to provide top-quality service to facilitate our clients’ therapeutic antiviral drug development.

The Mechanism of Mizoribine

Mizoribine, 4-carbamoyl-1-β-d-ribofuranosylimidazolium-5-olate, is an immunosuppressive agent used for renal transplantation, autoimmune diseases and steroid-resistant nephrotic syndrome. Mizoribine could be phosphorylated by adenosine kinase and converted to mizoribine 5-monophosphate, the active form of mizoribine. This activated form of mizoribine acts as an inhibitor of the enzyme, inosine 5-monophosphate dehydrogenase (IMPDH) and guanosine monophosphate synthetase. Both enzymes are essential to the synthesis of guanosine monophosphate from inosine monophosphate through the de novo pathway.

Antiviral Activities of Mizoribine

It has been demonstrated that mizoribine inhibits the replication of severe acute respiratory syndrome (SARS-CoV) in both plaque reduction and yield reduction assays. The inhibitory effect on the replication of SARS-CoV is virustatic rather than virucidal. Therefore, mizoribine may contribute to the further development of antiviral agents and therapeutic strategies for SARS-CoV. Moreover, mizoribine possesses in vitro anti-viral activities against diverse types of viruses, including respiratory syncytial virus, influenza virus, herpes simplex virus, cytomegalovirus, and bovine viral diarrhea virus. Considering the mechanism of mizoribine, this inhibitor can be potentially used in the treatment of 2019-CoV.

Fig.2 Cytotoxicity (A), inhibitory effect on plaque formation of SARS-CoV Frankfurt-1 (B) and HKU39849 (D) in a plaque reduction assay and inhibitory effect on the replication of SARS-CoV Frankfurt-1 (C) and HKU39849 (E) in yield reduction assay. The symbols, “●” and “■” represent mizoribine and ribavirin, respectively. (Saijo, 2005)

Mizoribine for the Treatment of SARS-CoV-2

Since mizoribine is currently used in several clinical applications and has not been associated with severe side effects, it is considered to be of potential use as a new anti-SARS-CoV-2 reagent, and it can be used in combination with other drugs. Creative Biolabs has established a powerful platform for antiviral drug discovery for SARS-CoV-2. Experienced in antiviral drug discovery, our scientists are pleased share to our knowledge and passion in the validation of mizoribine for the treatment of SARS-CoV-2.

Equipped with enriched experience, profound expertise and state-of-the-art instruments in antiviral drug discovery, Creative Biolabs offers top-quality validation service of mizoribine for the treatment of SARS-CoV-2. For more detailed information, please feel free to contact us or directly send us an inquiry.

Reference

1. Saijo, M.; et al. Inhibitory effect of mizoribine and ribavirin on the replication of severe acute respiratory syndrome (SARS)-associated coronavirus. Antiviral research. 2005, 66(2-3):159-63.

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