Korean researchers find Covid-19 oral drug candidates

Local researchers said they have found existing drugs that can be repurposed as an oral treatment for Covid-19.

On Thursday, a joint research team of the Korea Advanced Institute of Science and Technology (KAIST)’s Chemical and Biomolecular Engineering Department Professor Lee Sang-yup and Institut Pasteur Korea (IPK)’s Zoonotic Virus Laboratory Researcher Kim Seung-taek said they found three oral drugs that could be effective to treat Covid-19.

The three investigational anticancer drugs are omipalisib, tipifarnib, and emodin.

The research team established a drug repurposing strategy using virtual screening. Drug repurposing refers to finding new indications for FDA-approved drugs or investigational drugs in clinical trials that have already been tested for safety.

The research team applied a virtual screening approach to repurposing 6,218 FDA-approved and clinical trial drugs for Covid-19.

Also, the team developed an algorithm to automatically generate active structures of nucleotide analogs-based prodrugs, which are mainly used as antiviral drugs.

With the virtual screening platform, the research team separated 15 candidate compounds that inhibit the main protease that plays an essential role in the replication and proliferation of the Covid-19 virus and 23 candidate compounds that inhibit RNA-dependent RNA polymerase (RdRp).

Then, the researchers verified the effectiveness of the 38 drugs at IPK’s lab.

The results showed that seven out of 38 compounds showed efficacies in inhibiting the Covid-19 virus in kidney cells of a monkey infected with Covid-19 (Vero cells).

Three of these were also found to inhibit Covid-19 in human Calu-3 cells, the research team said.

The three Covid-19 treatment candidates are omipalisib, now being tested in a trial to treat cancer and idiopathic pulmonary fibrosis. Tipifarnib is in a trial to treat cancer and progeria, and emodin, a plant extract, in a trial as an anticancer drug.

Notably, the antiviral activity of omipalisib was 200-fold higher than that of remdesivir, the standard treatment for Covid-19. Tipifarnib was similar to remdesivir in antiviral activity.

The research team said one of the three-drug candidates showed toxicity. To find the optimal drug concentration that can be effective while minimizing toxicity, the research team plans to conduct a preclinical trial. The researchers will also run preclinical trials for the other two candidates.

“It is meaningful that we established a base technology to respond to a new virus outbreak quickly,” Lee said. “Based on this, we plan to develop a technology applicable to similar viruses of the Covid-19 virus family.”

The study, titled “Drugs repurposed for COVID-19 by virtual screening of 6,218 drugs and cell-based assay,” was published online in the Proceedings of National Academy of Sciences (PNAS) on Wednesday.