Peptide-based drugs could reduce severity of COVID-19

Queensland scientists have developed two new drugs that could prevent COVID-19 infection and stop further spread of the virus in patients who have already contracted it.

The research team at QIMR Berghofer has come up with two separate peptide-based drugs that could be available to patients within 18 months if trials are successful.

The drugs target the human cells’ response to the SARS-CoV-2 virus instead of the virus itself.

The findings of their research were published overnight in the journal Nature Cell Discovery.

Senior researcher at QIMR Berghofer Professor Sudha Rao said the first drug is designed to prevent infection and would be administered pre-exposure and aid the efficacy of vaccines, while the second drug would prevent the spread of the virus within cells.

“The first treatment works by blocking the virus from entering as it effectively acts like a padlock on the human cells,” she said.

“And the second drug, if the virus does enter, it prevents the virus from replicating.

“They are really what we call early intervention drugs, so they really are there to reduce the severity of the disease.”

Head of QIMR Berghofer's Gene Regulation and Translational Medicine Group, Professor Sudha Rao
Professor Sudha Rao says the drugs work in different ways to stop the virus. (Supplied: QIMR Berghofer Medical Research Institute)

The development of the drugs came after researchers uncovered a previously unknown way that SARS-CoV-2 entered cells and cause COVID-19.

“We know that the AC2 receptor is the critical entry point as to how the virus enters,” Prof. Rao said.

“What we’ve really uncovered is the way the virus is able to exploit the human cells and allow the AC2 door to become fully open, and therefore the virus can rapidly enter. 

“Once it enters it can use the cellular machinery in the human cells to replicate.

“And knowing that … one drug really acts like a cloak around the human cell and therefore prevents the virus from entering through the AC2 receptor.

“Whereas the second drug … if the virus does enter, the drug is specifically there to prevent the virus from replicating.”

‘We’re hoping to start clinical trials in a few months’
Laboratory tests have demonstrated that if the virus does infect a cell, the second drug is able to prevent the virus from ‘hijacking’ the host cell and replicating.

This boosts the immune system’s ability to recognise the virus.

Prof. Rao said the results of the laboratory testing were “looking very promising”.

“All our testing has been done in human cells and in gold-standard models of the SARS-CoV-2 virus, the COVID-19 models and, in both of those, what we’ve been able to show is that [these] drugs are very safe.

“We’re waiting on final results, because we are wanting to go very soon into human testing.

“We’re really hoping to start clinical trials in a few months,” she said.

Prof. Rao said they hoped the drugs would be effective against all variants of the virus. 

“The way that these drugs have been designed, they will be able to block all variants, all these betacoronaviruses.

“We have developed the drug against the region which is conserved amongst all the variants,” she said.

“So, it will be as effective against the variants as well.”

Although Queensland scientists are leading the research, it is an international collaboration.

“Even though we’re leading this, we’re part of an international consortium, and we are working with leaders in infectious diseases in Europe, where the COVID-19 disease is very rife … so there’s lots of patients,” Prof. Rao said.

“So it means that not only can we start the clinical trial, you want to be able to complete the clinical trial rapidly, so you can get it to as many people as possible.”

One of the tools that could help end pandemic
Professor Nabila Seddiki, who is testing the drugs at the Infectious Diseases Models for Innovative Therapies facility in France, said the development of the drugs was an exciting step in the fight against COVID-19.

“Many of the drugs being developed around the world to treat COVID-19 are targeted at people with severe disease,” Prof. Seddiki said.

“However, these peptide-based drugs are aimed at preventing infection in the first place, and at reducing the severity of the disease before it really takes hold.”

Prof. Rao said the production and distribution of the drugs would not be particularly difficult.

“One key aspect is that our drugs are stable at room temperature … so it means that they’re very stable,” she said.

“We’ve also even shipped them over to Europe, they’ve been on planes and so forth as well … so we know that they’re very stable, and they can be transported anywhere.

“The process of actually manufacturing the drugs is quite standard and straightforward, we can make large quantities of the drugs, so we don’t need lots of very, very specialist laboratories or anything like that. 

“So, we can manufacture large quantities of these drugs as well, which is also another advantage.”

Between the promising early trials, effectiveness against all variants and the relative ease of distribution, Prof. Rao said she could imagine some return to normality.

“This pandemic is here to stay,” she said.

“We’re going to need multiple tools in our toolbox and people are going to need multiple drugs and vaccines and different combinations to ensure that they’re safe.

“The hope that we have that through these sort of inventions – once we know the outcomes of human testing – that with these sorts of drugs together with vaccines that we can hopefully return back to where we were pre-COVID.”

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