A new study, looking at the replication stage of the coronavirus, discovered important mechanisms in its replication that could be the foundation for new antiviral therapies to address Covid-19.
The study, which set out to investigate how the SARS-CoV-2 virus replicates once it enters the cells, was carried out by the Kings College London researchers.
The majority of research into SARS-CoV-2 – the causative agent of COVID-19 – has focused on the Spike protein that allows viral entry. This has led to a lack of understanding of how the virus replicates once it has entered the cell.
A new paper led by Dr Jeremy Carlton in collaboration with Dr David Bauer at the Francis Crick Institute, focuses on how the Envelope protein of SARS-CoV-2 controls late stages of viral replication.
Published in Science Advances, the authors marked the Envelope protein with fluorescent tags to track its movement within cells and used proteomics to identify key pathways that allow SARS-CoV-2 to take over the internal compartments of the infected cell – known as organelles – for its replication.
The authors identified a surprising aspect of its replication in its use of a compartment called the lysosome during viral release. Lysosomes are acidic, degradative organelles, but SARS-CoV-2 uses its Envelope protein as an ion-channel to neutralise their acidity and so enhance viral release.
As well as broadening our theoretical understanding of the viral life cycle, such insights on replication could eventually be applied to create new antiviral therapeutics that inhibit the channel activity of the Envelope protein, say the authors of the study. These could apply not only to SARS-CoV-2, but to the ß-coronavirus family and any other virus that replicates with the same mechanisms.
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