The strategy of repurposing existing compounds to combat the new Coronavirus (SARS-Cov2) that causes COVID-19 is one that is being pursued on a global level. As SARS-CoV-2 is quite similar to SARS-CoV based on the full-length genome profile, existing SARS-CoV experimental data is being used to find a potential drug for SARS-CoV2. One of the compounds is Cyclosporin A, EvoPure® (C042). This product is a neutral, cyclic oligopeptide with immunosuppressive activity. Researchers at the Molecular Virology Lab at the Leiden University Medical Center in Leiden, the Netherlands were studying whether cytotoxicity as a result of Middle East Respiratory Syndrome (MERS-CoV) infection is a possible readout for antiviral screening. It was able to prevent MERS-CoV cytopathic effect in Vero and Huh7 cells. Infected cells were given Cyclosporin A or DMSO as a control, prior to infection. Cytotoxic effects caused by Cyclosporin A treatment alone were monitored in parallel plates containing mock-infected cells. They found Cyclosporin A acted as an inhibitor of MERS-CoV replication in cell culture. (de Wilde et al, 2013).
Low micromolar concentrations of Cyclosporin A affected the replication of SARS-CoV, human coronavirus 229E and mouse hepatitis virus in cell culture. Viral RNA and protein synthesis were almost undetectable, suggesting an early block in replication. Cyclosporin A can alter the function of many members of the cyclophilin family, which consists of peptidyl-prolyl isomerases that act as chaperones and facilitate protein folding. The compound was previously reported to inhibit replication of HIV, vesicular stomatitis virus (VSV) and Hepatitis C virus (de Wilde et al, 2011).
A research team at Rutgers University scanned microarray data for compounds that mimic the SARS-CoV Delta E top 10 genes. Surprisingly, they found that Cyclosporin A was a perfect match and upregulated all 9 upregulated genes and downregulated the only downregulated gene. Heat-shock proteins dominated the list of upregulated genes (HSP90AA1, HSP90AA1, UBB, DNAJB1, DNAJA1, HSPA8, UBC, DUSP1, BAG3). Downregulated gene was PPP2R5E. This means that Cyclosporin A can modulate the pathway involved in the cellular response to stress (Syad and Syad, 2020).
Our EvoPure brand has been highly purified to remove toxic impurities. Each product has been fully and carefully characterized by spectral analysis (HNMR, FTIR, MS and HPLC). If your research team would like to evaluate Cyclosporine A, EvoPure, as part of your research project for SARS-Cov2, please contact us (info@toku-e.com).
References
de Wilde AH et al (2013) MERS-coronavirus replication induces severe in vitro cytopathology and is strongly inhibited by Cyclosporin A or interferon-α treatment. J. Gen. Virol. 94(Pt 8):1749-1760 PMID 23620378 Link
de Wilde AH et al (2011) Cyclosporin A inhibits the replication of diverse coronaviruses.Gen. Virol. 92:2542-2548 PMID 21752960
Sayad S and Sayad S (2020) Cyclosporin A is a potential inhibitor of SARS-CoV-2. Link.