Monash researchers find key to blocking replication of COVID virus
Monash researchers have conducted extensive modelling of a new antiviral drug to show it has significant blocking ability against the virus that causes COVID-19.
To date, there is an absence of a vaccine and a lack of effective antiviral therapeutics against SARS-CoV-2, the virus causing COVID-19. Therefore, there is an intense interest in identifying compounds that may interact with key viral molecular targets, preventing infection or treating symptoms of the disease.
Dr Tom Karagiannis, from Monash University’s Central Clinical School, and his team recently published data in the Computational Biology Chemistry Journal, showing that a designer molecule called α-ketoamide blocks one of the key proteins needed by the SARS-CoV-2 virus to replicate.
Following the 2002 SARS outbreak, researchers in Germany designed compounds with broad-spectrum anti-coronaviral activity – called α-ketoamides. In May the same group published data on an “improved” version called α-ketoamide 13b which works more effectively in the human body.
Dr Karagiannis and his team have used the Pawsey supercomputer to study the way that α-ketoamide 13b blocks the triggering of replication of the SARS-CoV-2 virus.
They found that the molecule effectively blocks the active site of the main viral protease, putting a hand brake on the replication process. “This molecule stops the virus from replicating which can then stop the release of new virus particles and infection of other cells in the body,” Dr Karagiannis said.
Importantly the study found that α-ketoamide binds to the active site in a stable way and over a long period, making it a potentially very useful protection against infection with the COVID-19 virus.
α-ketoamide was initially developed for SARS and has been shown to work in many kinds of viruses, including enteroviruses and coronaviruses, because the active site of these proteases is highly conserved.
Currently, improvements are being made so that these molecules can be administered by inhalation to target the respiratory tract.
Liang J, Pitsillou E, Karagiannis C, Darmawan KK, Ng K, Hung A, Karagiannis TC. Interaction of the prototypical α-ketoamide inhibitor with the SARS-CoV-2 main protease active site in silico: Molecular dynamic simulations highlight the stability of the ligand-protein complex. Comput Biol Chem. 2020 May 28;87:107292. doi: 10.1016/j.compbiolchem.2020.107292.
19 June 2020 The Australian, "COVID-19 treatment found by computer" by Natasha Robinson. Link