Anti-HCMV activity by an irreversible p97 inhibitor LC-1310

Yan Wang, Ruben Soto-Acosta, Rui Ding, Liqiang Chen, Robert J. Geraghty

Research output: Contribution to journalArticlepeer-review

Abstract

The AAA+ (ATPase associated with various cellular activities) protein p97, also called valosin-containing protein, is a hexameric ring ATPase and uses ATP hydrolysis to unfold or extract proteins from biological complexes. Many cellular processes are affected by p97 including ER-associated degradation, DNA damage response, cell signaling (NF-κB), cell cycle progression, autophagy, and others. Not surprisingly, with its role in many fundamental cellular processes, p97 function is important for the replication of many viruses. We tested irreversible p97-targeting compounds for their ability to inhibit the replication of multiple viruses compared to the known p97 inhibitors NMS-873 and CB-5083. Our results indicate that overall cellular toxicity for p97 compounds provides a challenge for antivirals targeting p97. However, we identified one compound with sub-micromolar activity against human cytomegalovirus and improved cell viability to provide evidence for the potential of irreversible p97 inhibitors as antivirals. [Figure not available: see fulltext.]

Original languageEnglish (US)
Pages (from-to)440-448
Number of pages9
JournalMedicinal Chemistry Research
Volume30
Issue number2
DOIs
StatePublished - Feb 2021

Bibliographical note

Funding Information:
The authors wish to acknowledge the Center for Drug Design for support.

Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.

Keywords

  • Antiviral
  • Human cytomegalovirus
  • Valosin-containing protein
  • p97
  • p97 inhibitors

PubMed: MeSH publication types

  • Journal Article

Fingerprint

Dive into the research topics of 'Anti-HCMV activity by an irreversible p97 inhibitor LC-1310'. Together they form a unique fingerprint.

Cite this