Math Model Shows Combo-drugs Cepharanthine and Nelfinavir as Possible Treatment for COVID-19

Although vaccines are still being administered across the globe for COVID-19, the administration of the shots is not uniform across all countries. Even so, there are still so many unanswered questions for treatment and prevention of the virus. Will the recent vaccines work for variants as they arise? Will the vaccine work long term? How do we effectively treat those who contract the virus? And, what about those who cannot be given the vaccine? Given the number of unknowns, a team of researchers based in Japan, the US, and the UK launched a project to try to develop a possible treatment for COVID-19. Using mathematical models, their goal was simple, but not easy: find a possible (dare we say it?) cure for COVID-19. The results were published in the journal iScience.

They first established an experimental system for screening drugs that may help to control infections, using a type of cells called VeroE6/TMPRSS2 cells, which were manipulated to efficiently be infected with and produce SARS-CoV-2. “To determine whether a drug of interest could help combat infection by SARS-CoV-2, we simply had to expose VeroE6/TMPRSS2 cells to both the drug and SARS-CoV-2 and then observe whether the drug’s presence served to hinder the virus’s efforts to infect cells,” explains Professor Koichi Watashi from Tokyo University of Science.

They then screened a panel of drugs that are already approved for clinical use, many of which the medical community is familiar with for their use and controversy, including drugs like remdesivir and chloroquine. After extensive screening, the researchers found two drugs that provided effective SARS-CoV-2 suppression: cepharanthine, which is used to treat inflammation, and nelfinavir, which is approved for the treatment of HIV infection.

Results in summary for a possible treatment for COVID-19

Using computational models to predict that the combined cepharanthine and nelfinavir therapy could hasten the clearance of SARS-CoV-2 from a patient’s lungs, the researchers discovered the following:

  • Cepharanthine inhibited SARS-CoV-2 entry through the blocking of viral binding to target cells;
  • Nelfinavir suppressed viral replication partly by protease inhibition.
  • Consistent with their different modes of action, synergistic effect of this combined treatment to limit SARS-CoV-2 proliferation was highlighted.
  • Mathematical modeling in vitro antiviral activity coupled with the calculated total drug concentrations in the lung predicts that nelfinavir will shorten the period until viral clearance by 4.9 days and the combining of cepharanthine and nelfinavir enhanced their predicted efficacy.
  • These results warrant further evaluation of the potential anti-SARS-CoV-2 activity of cepharanthine and nelfinavir.
treatment for COVID-19 with cepharanthine and nelfinavir.
Mathematical modeling in vitro antiviral activity coupled with the calculated total drug concentrations in the lung predicts that nelfinavir will shorten the period until viral clearance by 4.9 days and the combining cepharanthine/nelfinavir enhanced their predicted efficacy.

Given that these drugs have distinct antiviral mechanisms, using both of them together could be potentially effective for patients. So, does this mean we will be seeing these new drugs in COVID-19 treatment centers?

Of course, the drug duo isn’t ready to be rolled out into healthcare systems just yet. These findings justify further research into the clinical potential of cepharanthine/nelfinavir therapy. The only conclusion the researcher can make is the drug combination is “useful and helpful.”

CONCLUSION/ Cepharanthine inhibited the entry of the virus into cells by preventing the virus from binding to a protein on the cell membrane, which it uses as a gateway. Nelfinavir worked to prevent the virus from replicating inside the cell by inhibiting a protein that the virus relies on for replication. Given the ongoing nature of the COVID-19 pandemic and the ever-increasing death toll, the development of cepharanthine/nelfinavir therapy may provide clinicians and patients with a much-needed new treatment option.

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Source: Hirofumi Ohashi, Koichi Watashi,Takaji Wakita, et al. Potential anti-COVID-19 agents, cepharanthine and nelfinavir, and their usage for combination treatment, iScience, Vol. 24, Issue 4, 2021, 102367.