TROY, N.Y. (NEWS10) – Rensselaer Polytechnic Institute researchers have secured a five-year, $3.5 million grant to develop a low-dose, oral COVID antiviral drug that can be administered at home. Rensselaer’s research is part of the consortium of a new antiviral drug development center, called the Center for Antiviral Medicines and Pandemic Preparedness (CAMPP).
CAMMPP will be led by Scripps Research. The center will be one of nine NIAID-sponsored Antiviral Drug Discovery (AViDD) Centers for Pathogens of Pandemic Concern.
The Rensselaer team will collaborate with Drs. Sumit Chanda and Arnab Chatterjee of Scripps Research Institute, Dr. Adolfo Garcia-Sastre of the Mount Sinai School of Medicine, and Dr. Stefano Ciurli of the University of Bologna, Italy. In research published in Cell Reports, the team found that in 10 of the hepatitis C drugs tested, seven suppressed the SARS-CoV-2 virus.
“Our role in the project is to develop novel inhibitors of the two key proteases of the SARS-CoV-2 virus, called CLpro and PLpro, which are essential to the virus life cycle,” said Rensselaer Polytechnic Institute researchers Gaetano Montelione.
The team’s work will build upon Dr. Montelione’s previous research. First, using bioinformatics, Dr. Montelione and his team found that a key protein from the hepatitis C virus closely resembles the coronavirus CLpro protease structure.
Three of those drugs were acting not only on the main protease, CLpro but on the PLpro protease, as well. Researchers additionally discovered that, when combined with the polymerase inhibitor remdesivir, these drugs multiplied remdesivir’s antiviral activity. Those that only inhibit CLpro did not amplify remdesivir’s effect.
“One of the big challenges is that the target will evolve to escape the drug,” Dr. Montelione said. “This is particularly problematic with rapidly mutating viruses like COVID-19. To overcome that, we try to hit multiple targets. By hitting both CLpro and PLpro simultaneously, there is less likelihood of antiviral resistance.”
Researchers anticipate that the most promising antiviral drugs to come out of the AViDD centers will enter late-stage preclinical development. Industry partners would provide valuable resources to accelerate their movement through the product development pipeline they said. Through already FDA-approved drugs for treating different diseases, that may be approved quicker for the treatment of COVID-19 virus.