The race to find an ideal drug, or a combination of drugs, which can counter the SARS-CoV-2 coronavirus, is on. Several scientists believe that existing drugs can be repurposed to treat COVID-19, thereby, saving valuable time and resources. Now, a new study states that two already-approved drugs can efficiently wipe out the notorious virus when used in combination.
According to the study by an international team of researchers, two drugs—Cepharanthine (CEP) and Nelfinavir (NFV)—were found to have strong inhibiting action against the novel coronavirus. The scientists also gleaned that the combination of the two drugs may have a potent effect against the pathogen and enhance the rate of its clearance from the body.
"In summary, our prediction shows the potential antiviral efficacy of NFV and CEP and its combined treatment that facilitates SARS-CoV-2 elimination," the authors wrote. The study was published in the journal iScience.
Turning to Existing Drugs
For the study, the authors established a cell-based drug screening system in order to identify compounds that could protect cells from the effects of the SARS-CoV-2 and help control the viral infection. The experimental screening system used cells called VeroE6/TMPRSS2 cells, which were made to be infected with SARS-CoV-2 and produce it.
"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," explained Dr. Koichi Watashi, corresponding author of the study, in a statement.
A panel of 306 drugs—that have been approved by multiple agencies for clinical use—were screened using the system. The screened drugs included drugs such as Chloroquine and Remdesivir, which have received approval for emergency use and trials for COVID-19 treatment. Among the evaluated compounds, two drugs—Cepharanthine and Nelfinavir—were found to effectively suppress SARS-CoV-2. While Cepharanthine is used for treating inflammation, Nelfinavir is an antiretroviral drug used for treating HIV infection.
The Power of Two
When the scientists tested Cepharanthine, the drug was found to inhibit the cellular entry of the SARS-CoV-2. It did so by preventing the coronavirus from binding with the protein—ACE2 (Angiotensin-converting enzyme 2)—found on the cell membrane, which it utilizes as a gateway into the cell. On the other hand, Nelfinavir prevented the replication of the SARS-CoV-2 within the cell by neutralizing a protein—main protease, or Mpro—that the coronavirus requires for multiplication.
As the two drugs have very different mechanisms of blocking the virus, the authors posited that the use of the compounds in combination with each other may prove effective in treating COVID-19 patients. In order to verify their theory, the team conducted In silico (computational models) tests. They tried to ascertain the potential antiviral efficacy of Cepharanthine and Nelfinavir individually, and together.
It was found that while they were efficient on their own, the combination of the two drugs may expedite viral clearance of SARS-CoV-2 from the lungs of COVID-19 patients by around 4.9 days. "These results warrant further evaluation of the potential anti-SARS-CoV-2 activity of Cepharanthine and Nelfinavir," the authors wrote. Hopefully, the development of therapy involving Cepharanthine and Nelfinavir may arm both clinicians and patients with a treatment option that effectively takes on the viral disease and enable quicker recovery.