Scientists hope small molecule anti-viral drugs could be used against Covid

Blood samples from coronavirus patients are prepared for analysis as part of the TACTIC-R trial, in the Blood Processing Lab
Blood samples from coronavirus patients are prepared for analysis as part of the TACTIC-R trial, in the Blood Processing Lab in the Cambridge Institute of Therapeutic Immunology and Infectious Disease, in Cambridge.

Scientists believe they may have discovered a new way to try and combat Covid-19 virus.

An international team from Bristol University believe that small molecule anti-viral drugs could be developed to help stop the virus from infecting human cells.

Sars-CoV-2 is the virus which causes Covid-19.

The scientists have found a “druggable” pocket within a Sars-CoV-2 spike protein which they hope could lead to new anti-viral drugs to shut down and eliminate the virus before it enters human cells.

They describe the findings, published in the Science journal, as a potential “game changer” in defeating the current pandemic.

Spike proteins, which are on the surface of the virus, are a key element for infections of the human cells.

The researchers found a small molecule, linoleic acid (LA), buried in a tailor-made pocket within the spike protein.

Linoleic acid (LA) is a free fatty acid, which is needed for many cellular functions and cannot be produced by the human body.

LA plays a vital role in inflammation and immunity levels, and it is also needed to maintain cell membranes in the lungs to help people breathe properly.

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 protein was generated allowing the researchers to peer deep inside the spike and identify its molecular composition.

The researchers spotted LA in a pocket within the spike 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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