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

In the present study, we analyzed the antiviral activity of pochonin D against HRV infection. Although pochonin D is a well-known Hsp90 inhibitor (Moulin et al., 2005; Wang et al., 2016; Choe et al., 2017) , it is still uncertain that the inhibition of Hsp90 by pochonin D is directly associated with the antiviral activity of it. We found that treatment with pochonin D lowered the level of pro-inflammatory cytokines in the lung and BALF of mice, which were increased by rhinovirus infection. Furthermore, the virus titers of HRV-infected mice treated with pochonin D were significantly decreased to levels similar to those in naïve mice. We also examined the levels of pro-inflammatory chemokines/cytokines (CCL2, CXCL1, TNF-α, IL-6, and IL-1β) in lung lysates and lung RNA. Their concentrations were decreased by pochonin D treatment in HRV1B-infected mice, and were comparable to the chemokines/cytokines levels in naïve mice. These data suggest that pochonin D may reduce inflammatory damage in rhinovirus-infected mice. We also found that neutrophil infiltration into the inflammatory site was reduced by pochonin D treatment in HRV1B-infected mice. This reduction may be due to the mild viral infection and inflammation in pochonin D-treated group. Finally, we observed the histopathology of the lung and airway, and found that pochonin D treatment ameliorated the damage induced by rhinovirus infection in the lung and airway.