Topoisomerase III (TOP3) Inhibitors and Antiviral Compounds based on Cyanine Dyes

Topoisomerase 3B (TOP3B) is the only topoisomerase that can act on RNA as well as DNA, and thus has been a target of interest for the development of cancer therapies and RNA viral infection therapies. In the context of cancer, TOP3B is not an essential gene, but a subset of cancer cells with pre-existing genome instability are particularly vulnerable to the inactivation of TOP3B. While inhibitors for other topoisomerases are among the most potent and widely used anticancer agents, there are no known inhibitors of TOP3B. In the context of RNA viral infections, TOP3B has been implicated as a host factor for the replication of positive strand RNA viruses, particularly flaviviruses (i.e., Zika, West Nile, and Dengue) and coronaviruses (i.e., SARS-Cov1 and -2). TOP3B RNA-cleavage complexes could be targeted and trapped by inhibitors, causing persistent RNA damage to block viral RNA replication. This mechanism resembles the one employed by inhibitors of topoisomerases 1 and 2, which block DNA replication of cancer cells. TOP3B inhibitors could thus be valuable RNA virus drugs and anticancer drugs. However, to date no TOP3B inhibitors have been approved for antiviral or anticancer applications.Researchers at the NIH (NCI and NIA) and their collaborators have discovered a family of cyanine dyes that could be used for anticancer and/or antiviral applications. The compounds have been shown to induce and stabilize TOP3B-RNA cleavage complexes in vitro and inhibit coronavirus replication...
Source: NIH OTT Licensing Opportunities - Category: Research Authors: Tags: Therapeutics Licensing Desired & Collaboration Desired Collaboration Sought NIA NCI Source Type: research