Preliminary research findings on PharmAust’s (ASX: PAA) lead candidates monepantel and monepantel sulfone have demonstrated that application of the drugs on human respiratory cells can inhibit the progression of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the virus responsible for COVID-19 infections.
The program at Melbourne’s Walter and Eliza Hall Institute of Medical Research has used the drugs on human Calu-3 lung adenocarcinoma epithelial cells in culture and showed virus particle counts of SARS-CoV-2 can be suppressed by between 90% and 95%.
The work needs to be repeated and receive robust verification before the research can progress to the next stage.
PharmAust has been working with the institute since April to test the effects of monepantel on the SARS-CoV-2 virus.
Vero cell line
The degree of anti-viral activity on Calu-3 cultures is believed to be similar to a previous evaluation of monepantel and monepantel sulfone in Vero cells from the kidney of an African green monkey, only at higher drug concentrations.
Non-human primate Vero cells are one of the more commonly used mammalian continuous cell lines in microbiology; however, they do not reflect how SARS-CoV-2 replicates and infects human tissue.
PharmAust said for this reason, it is important to test the effects of monepantel in human lung epithelial cells as well.
“It is important to also note that infectivity of human Calu-3 cells in culture may not necessarily reflect how SARS-CoV-2 infects and replicates in human organs under physiological conditions and how the constituent cells infected with SARS-CoV-2 react to treatment with monepantel and monepantel sulfone,” the company said.
“Sequential testing of [these drugs] through in vitro organoid and ex-vivo organotypic systems from patients of diverse ages, sexes and underlying disease conditions may be required to better understand how [they] affect SARS-CoV-2 infectivity prior to formalised clinical studies.”
PharmAust said clinical studies relating to monepantel and monepantel sulfone would be pursued as a matter of course, subject to the timely availability of organoid samples.
The company is aiming to produce a third run of GMP-grade monepantel tablets before year end to cater for future human trials.