btm said:
The original article was published in Nature Chemistry. The abstract’s available here:
https://www.nature.com/articles/s41557-018-0039-2
but the article itself is behind a paywall. Some excerpts from the abstract:
“Here we report the discovery of IMP-1088, a picomolar dual inhibitor of the human N-myristoyltransferases NMT1 and NMT2, and use it to demonstrate that pharmacological inhibition of host-cell N-myristoylation rapidly and completely prevents rhinoviral replication without inducing cytotoxicity.”
“We show that inhibition of the co-translational myristoylation of a specific virus-encoded protein (VP0) by IMP-1088 potently blocks a key step in viral capsid assembly,”
Looking to see if there are any similar articles by the same author RJ Leatherbarrow.
He’s been in charge of a department looking at foot and mouth disease for a while.
He’s written 23 other articles on myristoyltransferase. But they have been for work on parasite infections. Notably malaria (Plasmodium falciparum) Trypanosoma brucei and Leishmania major. eg. “N‐Myristoyltransferase: a Prospective Drug Target for Protozoan Parasites”, from 2008.
Branching into common cold rhinoviruses seems to be a completely new research area for him. So, nothing similar from RJ Leatherbarrow.
There is this PhD thesis by A Bell (2015). The title is funny N‐Myristoyltransferase as a Drug Target: A (Chemical) Space Odyssey.
Previous research has provided pre-‐clinical validation for inhibition of the enzyme N-‐myristoyltransferase(NMT) target as a novel treatment of fungal and parasitic infections. This thesis describes the discovery of novel NMT inhibitor series derived from high-‐throughput screens (HTS) of the Pfizer compound collection against NMTs from both Leishmania donovani and Plasmodium falciparum.
One possible candidate for therapeutic intervention is the human rhinovirus (HRV aka the common cold). HRV is a member of the picornavirus family (which also includes polio and foot and mouth disease), all of which feature an icosahedral capsid composed of 4 viral proteins (VP1-‐4) enclosing a single-‐stranded RNA genome . VP4 is known to be N-‐terminally myristoylated. In a “proof of concept” experiment (carried out by collaborators Roberto Solari,Aurelie Moustier and David Swieboda of the Airways Disease Infection group at the NHLI), the potent human NMTi, P56 was used to pre-‐treat HeLa cells 6h prior infection with the viral strain HRV16. The infected cells were left for 1h at room temperature then incubated overnight. In this assay format, the viral titre of living cells is determined at each dose level and is used to determine a tissue culture infected dose (TCID50) for P56 of ~20 nM (Figure 5.13). As has been demonstrated earlier with other NMTi, P56 had no effect on the host cells over the timescale of the experiment.
While recognising that there are safety concerns with the long-‐term use of inhibitors of human NMT due to its essentiality, the development of an NMTi for the treatment of a virus, such as the common cold, with acute effects over the limited time period would appear to be real possibility.
Aha, so there’s the connection. The common cold is of the same virus family as foot and mouth disease.