Extraordinary new images have documented exactly how the coronavirus SARS-CoV-2 attacks humans. A spike protein on the coronavirus is now understood to be the main weapon of attack for mobilising its viral DNA into a host cell.
The virus attacks and binds to the ACE 2 enzyme and is a critical step in how the virus spreads.
You can actually see that happen in real-time
Dr Kirill Gorshkov
Angiotensin-converting enzyme 2 (ACE2) receptors are human cell proteins capable of enabling such an attack.
With the help of bio-engineered quantum dots, Kirill Gorshkov and Eunkeu Oh at the Naval Research Laboratory (NRL) and their colleagues have, for the first time, managed to image this binding where this spike protein interacted.
Dr Gorshkov said: ”You can actually see that happen in real-time.
“That’s the beauty of this assay and that’s why we think it will be important for drug screening.”
A virus is known to be incapable of reproducing without enrolling a host cell.
As a result, scientists around the world are racing to understand how coronavirus interacts with and penetrates cells with the aim of blocking this stage to stop the onset of COVID-19 in its tracks.
Dr Gorshkov and his colleagues at NCATS were already using various imaging assays for cancers, viruses and lysosomal storage diseases.
However, Dr Gorshkov said: “When coronavirus hit, we quickly had to shift gears.”
Previous research into the related SARS coronavirus underlined the importance of interactions with ACE2 in human cells for the spread of this kind of virus.
This meant they were already able to tag these receptor proteins with a green fluorescent protein allowing them to image their movements.
Evidence was also accumulating to identify exactly which spike proteins on coronavirus can lock ACE2 into a stronghold so the deadly virus can enter the cell.
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However, spike protein interaction data has mostly been indirectly collected from biochemical or proximity assays and tests with proteins and parts of proteins taken from the virus, known as “pseudo-viro-particles.”
With no fluorescent labelling of these viral proteins, their role in the ACE2 receptor binding and internalisation – a process known as endocytosis – continued to work.
Scientists at NRL also attempted to use their nanoparticles knowledge for cellular delivery and bio-sensing to assist efforts in the search for drugs able to fight coronavirus.
Dr Oh began by examining potential ways of applying the protein-nanostructure conjugation techniques she had been working with.
With two proteins sharing a quantum dot known as a binding affinity attached to one and a fluorescing nanoparticle attached to the other.
The resulting binding between the two proteins will then bring nanostructures close enough for energy to transfer between them.
This allowed researchers to monitor the protein binding.
Dr Oh said: ”If you have any inhibitor in the middle to stop the binding, this can be used as an inhibition assay for drug screening, so we use this a lot.”
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