Chemistry:IMP-1088
IMP-1088 is an enzyme inhibitor of the human N-myristoyltransferases NMT1 and NMT2. It prevents the production of infectious virus particles by targeting host cell machinery rather than the virus itself. Specifically, it inhibits the host's NMT enzymes, blocking the myristoylation of viral proteins required for capsid assembly. Since this strategy acts on host proteins, it is thought to carry a lower risk of viral resistance.[1][2]
Antiviral activity
IMP-1088 blocks the replication of viruses that rely on myristoylated proteins for their life cycle, including poxviruses, mammarenaviruses, and rhinoviruses.[3][4][5] This approach has been explored for potential treatment of monkeypox, Lassa fever, and the common cold.
Mammarenaviruses
The inhibitor has demonstrated activity against mammarenaviruses such as LCMV and hemorrhagic fever viruses including Lassa and Junin. In these viruses, IMP-1088 targets myristoylated proteins such as the Z matrix protein and the signal peptide of glycoprotein 1, both essential for viral assembly, budding, and propagation.[4]
Poxviruses
In poxviruses such as vaccinia and monkeypox, inhibition of myristoylation disrupts the function of four essential myristoylated viral proteins. In combination therapies, this has been shown to completely inhibit viral replication.[5]
Research applications
In addition to its antiviral potential, IMP-1088 has been used as a research tool to study viral protein function. It has been shown that myristoylation and oligomerization are not required for the Z matrix protein’s dose-dependent inhibitory effect on viral ribonucleoprotein (vRNP) activity.[6]
References
- ↑ "Agent stops common cold virus replication". https://cen.acs.org/pharmaceuticals/drug-discovery/Agent-stops-common-cold-virus/96/i21?hootPostID=8a78f5ab938bf07977e9703b0a487e37.
- ↑ "A team of researchers may have actually found a cure to the common cold". Business Insider. 19 May 2018. http://www.businessinsider.com/researchers-may-have-actually-found-a-cure-to-the-common-cold-2018-5.
- ↑ "Fragment-derived inhibitors of human N-myristoyltransferase block capsid assembly and replication of the common cold virus". Nature Chemistry 10 (6): 599–606. June 2018. doi:10.1038/s41557-018-0039-2. PMID 29760414. Bibcode: 2018NatCh..10..599M.
- ↑ 4.0 4.1 "Cellular N-Myristoyl Transferases Are Required for Mammarenavirus Multiplication". Viruses 16 (9): 1362. August 2024. doi:10.3390/v16091362. PMID 39339839.
- ↑ 5.0 5.1 "Repurposing Drugs for Synergistic Combination Therapies to Counteract Monkeypox Virus Tecovirimat Resistance" (in en). Viruses 17 (1): 92. January 2025. doi:10.3390/v17010092. ISSN 1999-4915. PMID 39861882.
- ↑ "Mammarenavirus Z Protein Myristoylation and Oligomerization Are Not Required for Its Dose-Dependent Inhibitory Effect on vRNP Activity" (in en). BioChem 5 (2): 10. 2025-04-29. doi:10.3390/biochem5020010. ISSN 2673-6411. PMID 40520408.
 |  |
