Coronavirus Treatment: Nelfinavir, Cepharanthine Identified As Promising Multidrug Therapy Against SARS-CoV-2

Antiviral treatments targeting COVID-19 are urgently needed in this pandemic situation. The unprecedented spread of the deadly disease is forcing the researchers to evaluate existing therapies. Researchers have identified two new antiviral agents after screening a panel of already-approved drugs in a cell culture model of SARS-CoV-2.

Several drugs including ritonavir, chloroquine, lopinavir, favipiravir, and remdesivir have been repurposed in fighting COVID-19 and are all currently under evaluation.

The research team which identified this promising multidrug treatment for COVID-19 predicted that this new drug combination will prevent the coronavirus from reproducing by halting its transmission as well as disease progression.

Nelfinavir & Cepharanthine

The researchers from the National Institute of Infectious Diseases, Tokyo and collaborating universities are currently studying potential treatments for COVID-19 with this combination and the preliminary results appeared promising.

They screened a panel of over 300 drugs that have already been approved by the U.S. Food and Drug Administration (FDA) for use against several illnesses, including those that are currently under trials. The drugs were screened in a cell culture assay for coronavirus infection. The findings revealed that this drug combination had the most antiviral potential and that they were able to preserve cell viability 20 times more effective than others.

“These agents offer a promising new multidrug treatment to combat COVID-19 in comparison to many other currently explored candidates,” News Medical Life Science quoted the researchers.

How do these drugs work?

Nelfinavir inhibits the protease enzyme within the virus and prevents it from replicating. The second drug, cepharanthine, is an anti-inflammatory alkaloid drug extracted from the plants of genus Stephania.

They both work by a different mechanism and are synergistic, increasing their combined impact on the deadly novel coronavirus. While nelfinavir interacts with the main protease of the coronavirus and inhibits its replication, cepharanthine prevents it from attaching to and entering the cells. The findings suggested that both these drugs reduced the amount of viral RNA significantly, proportional to the dosage used. They also found that these drugs were effective without significant toxicity.

“Consistent with their different modes of action, in vitro assays highlight a synergistic effect of this combined treatment to limit SARS-CoV-2 proliferation. Mathematical modeling in vitro antiviral activity coupled with the known pharmacokinetics for these drugs predicts that Nelfinavir will facilitate viral clearance. Combining Nelfinavir/Cepharanthine enhanced their predicted efficacy to control viral proliferation, to ameliorate both the progression of disease and risk of transmission” said the researchers in their paper published in the journal bioRxiv.