Researchers from St Petersburg University, together with their colleagues from the Smorodintsev Research Institute of Influenza, have begun to create a protein drug that can block the spread of the SARS-CoV-2 virus in the upper respiratory tract. In the development, they use the protein domain of another coronavirus - HCoV-NL63, which is a less dangerous pathogen that causes seasonal acute respiratory viral infections. Both viruses attach to the cell using functionally similar protein fragments (RBD domains) and through the same ACE2 receptor. The scientists suggest: if the entrances to cells using the RBD domain of HCoV-NL63 are blocked, then SARS-CoV-2 will also not be able to get into them.
Сoronaviridae is a family of viruses that derives its name from the ‘solar corona’. Spikes on the surface of a viral particle create an image reminiscent of the corona. It is with the help of these ‘spike’ proteins that pathogens manage to enter human and animal bodies. They look for targets on the surface of healthy cells – receptors that they can catch hold of to enter the cell. In the case of the SARS-CoV-2 virus, which continues to scare the world’s population, the angiotensin-converting enzyme 2 (ACE2) becomes such a target. This receptor is involved in the regulation of blood pressure in the body.
‘Interestingly, another virus that is already known to human beings, coronavirus NL63, also interacts with the same receptor. It is much less dangerous and causes mild seasonal acute respiratory viral infections,’ said Anna Aksenova, the originator of the idea, a senior research associate at the Laboratory of Amyloid Biology, St Petersburg University. ‘Moreover, NL63, like SARS-CoV-2, uses ACE2 protein to enter the cell, and the very tip of its receptor-binding domain (RBD domain) – a kind of ‘hook’ that catches hold of the cell – attaches to the same area on the ACE2 surface as SARS-CoV-2. It means that we can try using a fragment of a weak virus to close the ACE2 receptor site, so that a strong virus could not also enter because the entry point would be occupied.’
The scientists explain that, to achieve this, it is necessary to develop a large amount of a blocking protein. A nasal or throat spray or eye drops would be created based on it. They will help prevent the spread of the new type coronavirus, which means they will help to treat and prevent COVID-19. According to the researchers, the protein drug should be used when the initial symptoms of the disease appear, as well as for those at high risk of infection. Theoretically, it can help stop SARS-CoV-2 even in the upper respiratory tract – before the viral particles get into the lungs. Even if pathogens can pass the barrier, then, as the scientists say, the infectious dose will be minimal and the body itself will be able to drive the disease off.
‘We are now at the outset of our research and are working to get a large amount of the applicable protein for further experiments,’ said Kirill Volkov, Director of the ‘Centre for Molecular and Cell Technologies’, a resource centre of the St Petersburg University Research Park. ‘To achieve this, we have obtained laboratory strains of Escherichia coli bacteria, which have a construct with a gene encoding the necessary fragment of the NL63 virus spike protein – expression strains. Our colleagues from the Smorodintsev Research Institute of Influenza have helped us get the sought-for part of the virus genome, and we have created expression plasmids. In the coming weeks, we will work over the isolation and purification of this protein from modified bacteria.’
The next steps of the research are: experiments in mice, which make it possible to see how toxic the drug candidate might be; and experiments in human cells. The scientists say that if the first results are promising, they will start to search for partners to conduct the first human trials. The first version of such a locally acting drug could be created in three to four months. This can be compared to the development of a vaccine against COVID-19, which, according to estimates of the World Health Organization, might take about a year and a half.