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Scientists find Covid-19 weakness which could be beaten with small molecule anti-viral drugs

EPA
EPA

A weakness has been detected in Covid-19's protein spike which means the strain could be injected with antiviral drugs to stop it working, scientists revealed.

An international team from Bristol University believe they have found a “druggable” pocket within a Sars-CoV-2 sample which could be a potential pandemic "game-changer".

The scientists hope the discovery could lead to small molecule, anti-viral medicines being developed to shut down and eliminate the virus before it enters human cells.

The study, which used insects cells, was published in the Science journal, with researchers saying the new knowledge, if applied correctly, could help defeat coronavirus.

The researchers found a small molecule, Linoleic acid (LA), buried in a tailor-made pocket within the spike protein which is located on the surface of the virus.

LA is a free fatty acid, which is needed for many cellular functions and cannot be produced by the human body. It also plays a vital role in inflammation and immunity levels, and it is needed to maintain cell membranes in the lungs to help people breathe properly.

A researcher studying Covid-19 (AFP via Getty Images)
A researcher studying Covid-19 (AFP via Getty Images)

Professor Imre Berger said: “Our discovery provides the first direct link between LA, Covid-19 pathological manifestations and the virus itself.

“The question now is how to turn this new knowledge against the virus itself and defeat the pandemic.”

The team used a powerful imaging technique, called an electron cryo-microscopy (cryo-EM), to analyse the Sars-CoV-2 spike.

A 3D structure of the Sars CoV-2 spike was generated allowing the researchers to peer deep inside the spike and identify its molecular composition.

The researchers spotted LA in a pocket within its protein.

Prof Berger described the research team as “truly puzzled” by the discovery and its implications.

Prof Berger said: “So here we have LA, a molecule which is at the centre of those functions that go haywire in Covid-19 patients, with terrible consequences.

“And the virus that is causing all this chaos, according to our data, grabs and holds on to exactly this molecule – basically disarming much of the body’s defences.”

The team have found hope from previous studies on the rhinovirus, which is a virus that causes the common cold.

They said that a similar pocket was exploited to develop potent small molecules which were successfully used as anti-viral drugs in human trials in a clinic.

The Bristol team hopes that a similar strategy can now be used to develop small molecule anti-viral drugs against Sars-CoV-2.

Prof Nicola Stonehouse, a professor in molecular virology at Leeds University, said: “One of the concerns regarding controlling the current Sars-CoV-2 pandemic is the lack of antiviral drugs that specifically target the virus.

“This detailed study defines a pocket in the spike and hence generates very useful data as this could lead to the design of antiviral drugs in the future.

“However, it should be noted that the material used here was made in insect cells, which might be a limitation, and that drug design/screening would be needed in order to select candidate drugs, but it’s a very positive step in the right direction.”

Prof Melanie Welham, executive chair of the Biotechnology and Biological Sciences Research Council, said the study had produced “fascinating findings”, which could be “vital as we seek ways to control and defeat the virus”.

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