Medication shown to inhibit virus from infecting cells and replicating.
Investigators from the Virginia Commonwealth University (VCU) Massey Cancer Center are reporting an experimental cancer drug called AR-12 kills SARS-CoV-2.
The discovery was made by a team of scientists at Massey and led by Paul Dent, PhD, professor in the VCU Department of Biochemistry and Molecular Biology and the Universal Corporation Chair in Cancer Cell Signaling and a member of the Cancer Cell Signaling research program at Massey, Their findings were published online in the journal Biochemical Pharmacology.
“AR12 is a derivative of celecoxib which no-longer acts against COX2 but instead inhibits the ATPase activity of multiple chaperone proteins, in particular GRP78. GRP78 acts as a sensor of endoplasmic reticulum stress and is an essential chaperone required for the life cycle of all mammalian viruses,” wrote the investigators.
The experimental therapy has been studied as a cancer and antiviral drug. Dent and other investigators have published findings showing it to be effective against viruses including Zika, mumps, measles, rubella, chikungunya, RSV, CMV, drug resistant HIV, and influenza.
"AR-12 works in a unique way. Unlike any other anti-viral drug, it inhibits cellular chaperones, which are proteins that are required to maintain the right 3D shape of viral proteins. The shape of the virus is critical to its ability to infect and replicate," Dent said.
For the SARS-CoV-2 research, Dent has worked with Jonathan Rayner, PhD, at the University of South Alabama and Laurence Booth, PhD, from Dent's lab.
Andrew Poklepovic, MD, member of the Developmental Therapeutics research program and medical director of the Clinical Trials Office at Massey is leading efforts to translate these findings into a clinical trial.
AR-12 has been shown to be safe and well-tolerated in a previous clinical trial, and is an oral therapy giving it an added benefit.
"Most COVID-19 drugs are given intravenously, so this would be a unique therapeutic option and potentially suitable for outpatient therapy, similar to the way one would take an antibiotic," Poklepovic said.