The Dream Team: Scientists Find Drug Duo That May Cure COVID-19 Together

Preclinical experiments show that the drugs cepharanthine and nelfinavir may be effective treatments for COVID-19

While preventative care for COVID-19 has made much noise (with vaccines having rolled out in most countries), the soaring infection rates indicate the need for effective treatments. Using cultured cells to study SARS-CoV-2 infections, researchers at the Tokyo University of Science and other institutions have discovered that the drugs cepharanthine and nelfinavir are effective at combating the virus, with the former preventing the virus from entering cells and the latter preventing the virus from replicating.

Researchers screened a panel of drugs that are already approved for clinical use and identified two drugs that provided effective SARS-CoV-2 suppression: cepharanthine and nelfinavir | Photo credit: Louis Reed on Unsplash
Researchers screened a panel of drugs that are already approved for clinical use and identified two drugs that provided effective SARS-CoV-2 suppression: cepharanthine and nelfinavir | Photo credit: Louis Reed on Unsplash

COVID-19 continues to claim lives across the world and is infecting millions more. Although several vaccines have recently become available, making significant strides towards preventing COVID-19, what about the treatment of those who already have the infection? Vaccines aren’t 100% effective, highlighting the need — now more than ever — for effective antiviral therapeutics. Moreover, some people can’t receive vaccines due to health issues, and new variants of SARS-CoV-2, the virus that causes COVID-19, that can penetrate vaccine-conferred immunity, are being reported, indicating that we need to think beyond prevention.

Given this need, a team of researchers based in Japan, the US, and the UK launched a project to develop effective therapeutics. This team included several researchers based at Tokyo University of Science: Visiting Professor Koichi Watashi, Dr. Hirofumi Ohashi, Professor Shin Aoki, Professor Kouji Kuramochi, and Assistant Professor Tomohiro Tanaka. Their goal was clear and simple: finding a cure for COVID-19.

To achieve this goal, the researchers first established an experimental system for screening drugs that may help to control infections. This system used 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 Watashi.

The researchers used this experimental system to screen a panel of drugs that are already approved for clinical use, including drugs like remdesivir and chloroquine that have already being approved or are being trialed as treatments for COVID-19. In an exciting outcome, 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.

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. In contrast, nelfinavir worked to prevent the virus from replicating inside the cell by inhibiting a protein that the virus relies on for replication. Given that these drugs have distinct antiviral mechanisms, using both of them together could be especially effective for patients, with computational models predicting that combined cepharanthine/nelfinavir therapy can hasten the clearance of SARS-CoV-2 from a patient’s lungs by as few as 4.9 days.

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, and only following this can we say for sure that it is useful and helpful.

Nevertheless, 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.

Reference

Title of original paper: Potential anti-COVID-19 agents, cepharanthine and nelfinavir, and their usage for combination treatment

Journal: iScience

DOI: https://doi.org/10.1016/j.isci.2021.102367

About The Tokyo University of Science

Tokyo University of Science (TUS) is a well-known and respected university, and the largest science-specialized private research university in Japan, with four campuses in central Tokyo and its suburbs and in Hokkaido. Established in 1881, the university has continually contributed to Japan’s development in science through inculcating the love for science in researchers, technicians, and educators.

With a mission of “Creating science and technology for the harmonious development of nature, human beings, and society”, TUS has undertaken a wide range of research from basic to applied science. TUS has embraced a multidisciplinary approach to research and undertaken intensive study in some of today’s most vital fields. TUS is a meritocracy where the best in science is recognized and nurtured. It is the only private university in Japan that has produced a Nobel Prize winner and the only private university in Asia to produce Nobel Prize winners within the natural sciences field.

Website: https://www.tus.ac.jp/en/mediarelations/

About Professor Koichi Watashi from Tokyo University of Science

Dr. Koichi Watashi is the Director of the Division of Drug Development, Research Center for Drug and Vaccine Development, at the Japanese National Institute of Infectious Diseases and a Visiting Professor at the Tokyo University of Science Graduate School of Science and Technology. His main research interests include virus-host interaction mechanisms and the development of antivirals. He has authored more than 140 papers in peer-reviewed scientific journals, and he has received several prestigious professional awards from organizations such as the Japanese Cancer Association, the Japanese Society for Virology, and the Japanese Society of Hepatology.

About Dr. Hirofumi Ohashi from Tokyo University of Science

Dr. Hirofumi Ohashi, the first author of this paper, is a researcher affiliated to the Department of Virology II, National Institute of Infectious Diseases, and the Department of Applied Biological Sciences, Tokyo University of Science. He has authored 18 papers in peer-reviewed scientific journals, and he has received awards from International Symposium on Hepatitis C Virus and related viruses. His key research interests focus molecular biology of positive-strand RNA viruses, mainly SARS-CoV, SARS-CoV-2, and the hepatitis C virus.

Funding information

This work was supported by the Japanese Agency for Medical Research and Development, the Japan Society for the Promotion of Science, the Japan Science and Technology Agency, and the Wellcome Trust.

Media contact

Tsutomu Shimizu

Email: mediaoffice@admin.tus.ac.jp

Tokyo University of Science (TUS) is one of the most well-known, respected, and the largest science-specialized private research universities in Japan.

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