Top News

Using Polyuridine Sequences In Mouse Coronaviruses, You Can Inhibit Host Cell Death

In the wake of the global spread of coronavirus infection (COVID-19), vaccination against its causing pathogen, the highly virulent acute respiratory infection coronavirus 2 (SARS-CoV-2) are offering encouragement that life may soon get back to “normal”.

Besides seeking new drugs that can mitigate severe or critical COVID-19, there is also a great need to prevent death. Particularly concerning is the lack of vaccine access in areas of the world where the cost of vaccines has been alarmingly high.

Using Polyuridine Sequences In Mouse Coronaviruses, You Can Inhibit Host Cell Death

In what way does this study matter?

Numerous different SARS-CoV-2 strains have risen and seem to have demonstrated a higher threshold of infectivity, reduced neutralization by vaccinations or previous exposure, and potentially even increased infectiousness. An interesting new preprint describes a proof of concept for the identification of novel targets specific to viruses, which could provide a broad-based pharmaceutical intervention. Viruses with positive-sense genomes of ribonucleic acid (RNA) are known as SARS-CoV-2.

Using Polyuridine Sequences In Mouse Coronaviruses, You Can Inhibit Host Cell Death

Presently, this report is formed using a synthetic oligonucleotide of deoxyribonucleic acid (DNA) to attach to the polyadenine 5′-PolyU tract in the mouse coronavirus (MHV-A59). The reduction of cell deaths observed in mouse cells infected with MHV-A59 following treatment with this molecule was remarkably significant.

A new drug to inhibit Coronavirus infection within host cells may be developed based on this unique mechanism of action against this virus. It is probably possible to extend this to SARS-CoV-2 as well. The 5′-PolyU tract is found in all infected cells shortly after viral entry, so it may serve as a biomarker for infection detection early in the infection process.

Placing a target on the PolyU tract

Vaccine shortages have contributed to a growing gap between vaccine possessors and those who lack them. In some countries, vaccines are being administered in two-dose regimens as much as possible, and the second dose is being delayed until supplies are sufficient. This may provide a broader net of partial immunity, but it could also provoke the emergence of new immune-escape variants, many of which might be pathogenic or more transmissible.

Mutations in genomic coding regions of SARS-CoV-2 may render these drugs ineffective as well. A possible alternative would be to design or modify drugs that would inactivate sections of viral genomes essential for viral replication. Such drugs would be extremely unlikely to develop resistance by mutation, making the development of new escape variants impossible when drugs or vaccines are selected.

As a result, this type of strategy effectively prevents escape variants from being created. This study examined the tract comprising five polyuridine nucleotides (5′ poly-U) found in the antigenome (minus RNA genome) of good-sense viral RNA. PolyU tracts, which are required as templates to generate positive-sense strands’ 3′-PolyA tails, come from 5′ PolyU tracts.

A mutation in this PolyU tract is almost certain to stop this synthesis, which subsequently prevents the replication of the viral genome, thus blocking the completion of the virus’ life cycle. In previous studies, the existence of the 5′-PolyU tract on this antigenome strand was firmly established as critical to the survival and infectivity of positive-sense RNA viruses.

You might read also: BioFit reviews

Furthermore, host cells do not have the 5′-PolyU tract completely, assuring viruses that they aren’t able to target it. While RNA polymerase III does play an important role in the transcription of some small RNA molecules, scientists are working to distinguish it from viral 5′-PolyU to prevent side effects from drugs. The polyA tail also stabilizes and matures the immature strand of the positive-sense RNA from which it is derived. Despite oligo-5′-PolyU binding possibly simulating an immune escape by reducing the length of the 5′-PolyU stretch, it may prevent viral particles from having completed formation. We will need to do more research to discover the mechanisms through which cell death occurs.

Click to comment

Leave a Reply

Your email address will not be published. Required fields are marked *

To Top