27th Aug 2020
27th Aug 2020
Curated by Simon Chapman
When coronaviruses, like the one causing COVID-19, multiply, their genetic material unwinds from a “coiled state” before it’s copied. This could be used against the virus, as this process sometimes results in an error.
The coil –the genetic blueprint for replication – can misfold into unusual shapes. Since the world is still waiting for a COVID-19 vaccine, any treatment that can slow down the spread of infection would be welcome. However, our group’s investigation into these “faulty” structures suggests that these naturally occurring errors don’t exist long enough to cause a problem in viral replication on their own.
How can we exploit this weakness? Finding a way to extend the lifetimes of these misfolded states might potentially slow down the speed of replication of SARS-CoV-2. How do we do this? Normally, the genetic code is read after the virus has entered a host cell. Bit by bit, the RNA sequence of the virus transfers its information and kickstarts a series of chemical events within the host cell. Hence, if we want to damage the virus, it makes sense to target the unwound RNA right at the start of this process. Recent studies have found that geometrical complexes can form by folding of specific viral RNA sequences. To test the idea, we have applied this finding to a region of the SARS-CoV-2 viral blueprint that consists of similar sequences. Using an advanced computer technique our data strongly suggests that these ‘misfolded complexes’ (atoms lined up in geometrical shapes) could arise in 20% of the cases during SARS-CoV-2 replication, but these states probably don’t last long. To stabilise the problematic structures we could use several approved drugs. These bind to similar ‘complexes’ in RNA, disabling the error-correcting mechanism in the virus. The next step in our research would be to trial these repurposed drugs in computer simulations and look for any effects that might increase the complexes’ lifetime. If we identify the right candidates, we could get closer to messing up the replication mechanism of the virus and thus gain the power to stop or slow down its spread.*
Here is the current state of science on a Sparrho pinboard.
*Please note: This FAQ is explaining an ongoing early-stage research project, with the hypothesis still being tested and not proven yet.
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PhD Student at The Open University (OU), UK. Simon has a background in Medicinal Chemistry and Molecular Biology. His doctoral research explores non-canonical molecular structures in Nucleic Acids and the role of specific co-ordinating cations. The aim is to apply the work in a biological context and suggest potential chemotherapies.