Related Experiment Video
Updated: Jun 25, 2026
Development of Cell-type specific anti-HIV gp120 aptamers for siRNA delivery
Published on: June 23, 2011
Inhibition of Simian Virus 40 replication by targeting the molecular chaperone function and ATPase activity of T
Christine M Wright1, Sandlin P Seguin, Sheara W Fewell
1Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260, USA.
Abstract:
Polyomaviruses such as BK virus and JC virus have been linked to several diseases, but treatments that thwart their propagation are limited in part because of slow growth and cumbersome culturing conditions. In contrast, the replication of one member of this family, Simian Virus 40 (SV40), is robust and has been well-characterized. SV40 replication requires two domains within the viral-encoded large tumor antigen (TAg): The ATPase domain and the N-terminal J domain, which stimulates the ATPase activity of the Hsp70 chaperone. To assess whether inhibitors of polyomavirus replication could be identified, we examined a recently described library of small molecules, some of which inhibit chaperone function. One compound, MAL2-11B, inhibited both TAg's endogenous ATPase activity and the TAg-mediated activation of Hsp70. MAL2-11B also reduced SV40 propagation in plaque assays and compromised DNA replication in cell culture and in vitro. Furthermore, the compound significantly reduced the growth of BK virus in a human kidney cell line. These data indicate that pharmacological inhibition of TAg's chaperone and ATPase activities may provide a route to combat polyomavirus-mediated disease.
Insights
A novel compound, MAL2-11B, effectively inhibits polyomavirus replication by targeting the viral large tumor antigen
Area of Science:
- Virology
- Molecular Biology
- Drug Discovery
Background:
- Polyomaviruses, including BK virus and JC virus, are associated with diseases, yet effective antiviral treatments are scarce due to challenges in virus culturing.
- Simian Virus 40 (SV40) replication is well-understood and serves as a model for studying polyomavirus replication mechanisms.
Purpose of the Study:
- To identify small molecules that can inhibit polyomavirus replication.
- To investigate the potential of targeting viral large tumor antigen (TAg) chaperone and ATPase activities for antiviral therapy.
Main Methods:
- Screening a library of small molecules for inhibitors of SV40 replication.
- Assessing the effect of compounds on TAg's ATPase activity and Hsp70 chaperone activation.
- Evaluating viral propagation and DNA replication in cell culture and in vitro.
- Testing compound efficacy against BK virus in human kidney cells.
Main Results:
- One compound, MAL2-11B, demonstrated inhibition of TAg's ATPase activity and Hsp70 activation.
- MAL2-11B significantly reduced SV40 propagation and DNA replication.
- The compound also effectively inhibited BK virus growth in human kidney cells.
Conclusions:
- Pharmacological inhibition of TAg's chaperone and ATPase activities is a viable strategy for developing novel antiviral treatments against polyomaviruses.
- MAL2-11B shows promise as a potential therapeutic agent for polyomavirus infections.
More Related Videos
13:13Single-cell Quantitation of mRNA and Surface Protein Expression in Simian Immunodeficiency Virus-infected CD4+ T Cells Isolated from Rhesus macaques
Published on: September 25, 2018
05:22Electrophoretic Analysis of Replication Through Structure-Prone DNA Repeats Within the SV40-Based Human Episome
Published on: September 13, 2024
Related Concept Videos
01:19Inhibitors of Virion Maturation and Assembly
01:30Inhibitors of Viral Protein Synthesis
01:25Inhibitors Of Virion Release
01:22Antiviral Nucleoside Inhibitors