The Dublin-based biotech’s focus is now on peptides that exhibit antiviral and cytokine regulatory properties with the goal of creating a therapeutic peptide ‘cocktail.’
With the aid of a grant from the Partnership for Advanced Computing in Europe (PRACE), this peptide blend could lessen viral replication and modify the inflammatory reaction that contributes to respiratory damage in coronavirus patients.
“It is obvious that more than one solution may be needed to mitigate the impact of the COVID-19 pandemic,” says Nora Khaldi, Nuritas’ founder and chief executive officer.
“The Nuritas team is eager to leverage our proprietary AI platform, which integrates vast quantities of data with strong scientific capabilities, to identify therapeutic peptides with the potential to address two key drivers of disease progression.”
Headed up by Nuritas’ Dr Hansel Gómez Martínez, the six-month project is backed by the PRACE Fast Track Call for Proposals that awards computing resources to contribute to lessening the impact of the current pandemic.
With substantial use of the Piz Daint supercomputer hosted by the Swiss National Supercomputing Centre (CSCS) awarded to Nuritas, the project describes the progress made and what could be expected in due course.
“We have identified already six targets from the virus with experimental structures available: SARS-CoV-2 Spike protein, main protease, nucleocapsid protein, non-structural proteins (NSP) 3, NSP10 and NSP15,” the project’s description states.
“We will extend that list as more structures become available or homology modelling is feasible. In fact, the 30kb genome of SARS-CoV-2 encodes as many as 16 non-structural proteins (Nsp1-16).”
Along with the natural peptide cocktail, the description goes on to state that this blend may also provide some universal protection against other viruses of the same family since similar coronaviruses use comparable infection mechanisms.
“Modulating inflammation is relevant in any infectious process, including COVID-19,” the project adds.
“Therefore, we could include these peptides to alleviate symptoms, like inflammation, which are tightly associated to the pneumonia and eventual mortality of patients.”
Evidence of antimicrobial action of one of Nuritas’ patented peptides (NuriPep 1653) was featured in a recent study by the firm in which the peptide, extracted from the pea plant proteome, demonstrated bacteria-killing properties against a multidrug resistant clinical strain of Acinetobacter baumannii.
This strain is considered an opportunistic pathogen in humans, affecting people with compromised immune systems, and is recognised as a hospital-derived infection.
Antimicrobial peptides appear to be viable alternatives to antibiotics based on their low tendency for inducing resistance and their broad-spectrum activity based on a general mechanism of action.
These peptides appear to directly kill bacteria either via membrane or non-membrane targeting and less observed, by immune modulation.
These mechanisms means they are often active against both antibiotic susceptible and resistant bacteria, which places them competitively among new antimicrobial solutions for the pharmaceutical sector.
"Peptides are naturally suited to address infectious diseases, as they can disrupt protein-protein interactions,” explains Nigel Stevenson, assistant professor of viral immunology at Trinity College Dublin
“For example, if peptides were discovered to inhibit SARS-CoV-2 from interacting with cellular proteins, they could certainly help in our fight against COVID-19,” adds Dr Stevenson who has been studying the effects of coronaviruses, SARS and MERS upon the anti-viral immune response for several years.
Dr Stevenson also says that the immunology research team at Trinity, together with collaborators in the United States and Hong Kong, are discovering that coronaviruses use a conserved mechanism to block innate immune responses and are pursuing these investigations towards the development of novel therapeutics for COVID-19.
"In addition, the super-computing strength, associated with artificial intelligence platforms, such as that utilised by Nuritas is fundamental in accelerating therapeutic peptide identification,” he adds.