Antiviral and Anti-Inflammatory Activities of Pochonin D, a Heat Shock Protein 90 Inhibitor, against Rhinovirus Infection

Song, Jae-Hyoung; Shim, Aeri; Kim, Yeon-Jeong; Ahn, Jae-Hee; Kwon, Bo-Eun; Pham, Thuy Trang; Lee, Jongkook; Chang, Sun-Young; Ko, Hyun-Jeong

Generally, virus-specific proteins have drawn attention for the treatment of viral infection as targets. However, the focus of antiviral approaches has recently started to move toward targeting host factors essential to virus multiplication. Hsp90, a molecular chaperone that regulates the function, turnover, and trafficking of several proteins including signaling and regulatory proteins, is one of the important host factors that play critical roles in the viral life cycle. Hsp90 inhibitors have been reported to inhibit Ebola virus (EBOV) replication, and cause degradation of the viral polymerase (Smith et al., 2010) . However, the exact mechanism underlying the anti-EBOV activity of Hsp90 inhibitors remains unknown. In influenza virus infection, Hsp90 is required for viral genome replication. As Hsp90 associates with subunits of the influenza virus, inhibition of Hsp90 leads to degradation of viral subunits. Besides, Hsp90 inhibitors reduce the levels of the assembled polymerase complex, resulting in decreased viral RNA levels (Momose et al., 2002) . A recent study showed that Hsp90 is also required for the replication of beta-herpesviruses (Burch and Weller, 2005) . In the human cytomegalovirus infection model, Hsp90 inhibition resulted in degradation of the viral polymerase and reduction of viral gene expression via downregulation of the PI3-kinase pathway (Basha et al., 2005) . Similarly, in the flock house virus, Hsp90 influences RNA polymerase stability (Kampmueller and Miller, 2005) . Collectively, pharmacological inhibitors of Hsp90 have potential as broad spectrum antiviral agents. In addition to their universal activity against diverse viral infections, Hsp90 inhibitors show the possibility of overcoming viral drug resistance. Most antiviral agents lead to generation of drug-resistant variants, which is one of the major issues in the development of effective antiviral therapy (zur Wiesch et al., 2011) . Interestingly, Hsp90 inhibitors are not reported to induce viral drug resistance till date. Therefore, they might be particularly useful for antiviral therapy against viruses prone to develop drug resistance (Geller et al., 2012) .