Researchers Scramble to Make COVID-19 Manageable with Antivirals

Vaccines against COVID-19 were developed in record time, but the successful advancement of therapeutics, particularly those that could disrupt the CARS-CoV-2 virus cycle, have been slower to move through the clinic. Researchers at multiple companies and institutes are doggedly pursuing that goal so the virus can become little more than a hindrance in the future.

A recent PBS report highlighted some of these efforts, focusing on clinical programs that have the potential to halt viral reproduction and keep those infected out of the hospitals. Experimental medications such as molnupiravir, in development by Merck and Florida-based Ridgeback Biotherapeutics, have the potential to fill the treatment gaps that vaccines cannot. Merck and Ridgeback are jointly developing molnupiravir, an orally available antiviral candidate for the treatment of COVID-19.

Earlier this year, the two companies noted a slight setback in the development of that program. In April, Merck announced it was moving molnupiravir into the Phase III portion of the Phase II/III MOVE-OUT study in outpatient COVID-19 patients based on a planned interim analysis from the Phase II part of the study. However, at the time, the companies said the Phase III portion of another study, the Phase II/III MOVE-IN study in hospitalized patients, will not proceed due to data that suggests molnupiravir is unlikely to demonstrate a clinical benefit in that patient population.

Daria Hazuda, vice president of infectious disease and vaccine discovery research at Merck, said they are hopeful the Phase III portion of the study, expected to be complete later this year, will demonstrate that molnupiravir is an effective treatment for mild to moderate cases of COVID-19. 

Beyond Merck, PBS noted research conducted by Adolfo Garcia-Sastre, the director of the Global Health and Emerging Pathogens Institute at Icahn School of Medicine at Mount Sinai and the University of California, San Francisco’s Quantitative Biosciences Institute. After extensive research on multiple antiviral options, the collaborators put their focus on plitidepsin, an injectable multiple myeloma drug medicine developed by Spain’s PharmaMar. Plitidepsin acts by blocking the protein eEF1A, present in human cells, which SARS-CoV-2 uses to reproduce and infect other cells. Through this inhibition, the expectation is that reproduction of the virus inside the cell is prevented, making this propagation to the rest of the cells unviable. 

Phase III research of plitidepsin was greenlit by Spanish health authorities last month. The scientific team hopes to see if the oncology drug effectively reduces days in the hospital for COVID-19 patients.

In its report, the results of compare plitidepsin’s effectiveness in the Phase III study would be compared to Gilead Sciences’ remdesivir, which is currently the standard of care for COVID-19. Remdesivir, the only antiviral approved to treat COVID-19, can shorten the hospital stay of COVID-19 patients, it has fallen short in treating patients. Garcia-Sastre told PBS he hopes plitidepsin will demonstrate live-saving potential.

Another potential antiviral highlighted by the news outlet is ivermectin, a decades-old drug approved to treat head lice infections as well as the treatment of some parasitic worms. Research has shown in a laboratory setting that the use of ivermectin inhibited the SARS-CoV-2 virus within 24 to 48 hours of treatment. The preclinical data showed that ivermectin prevented the virus’ RNA from replicating. While COVID-19 is not a parasitic disease, the laboratory tests showed that the drug targets the disease like one.