A study conducted by researchers from Sapienza University of Rome and the National Institute for Infectious Diseases, Lazzaro Spallanzani IRCCS, has revealed a surprising link between certain cancer drugs and an increased susceptibility to SARS-CoV-2 infection in lung cells. The study focused on the impact of histone deacetylase (HDAC) inhibitors, commonly used in cancer therapy, on the replication and infection dynamics of SARS-CoV-2.
The researchers discovered that HDAC1-3 inhibitors, particularly MS-275, significantly increased the expression of ACE2 and TMPRSS2 receptors, which play a crucial role in SARS-CoV-2 entry. This unexpected finding suggests that HDAC inhibition might promote SARS-CoV-2 infection.
Further experiments confirmed the heightened receptor expression and demonstrated that MS-275 could enhance SARS-CoV-2 replication in certain cell lines. The study also provided insights into the molecular mechanisms by which MS-275 treatment increased the transcription of ACE2 and TMPRSS2.
The researchers discussed the broader implications of these findings in the context of epigenetics and the pathogenesis of SARS-CoV-2. They highlighted the intricate modulation of ACE2 and TMPRSS2 expression, which are essential for viral entry into host cells. The study challenged previous research by showing that most tested HDAC inhibitors increased ACE2 and TMPRSS2 expression, with MS-275 and MGCD0103 being the most potent inducers.
The discussion section also explored the potential effects of HDAC inhibitors on viral infectivity, inflammatory cytokine production, and immunomodulation. The study raised concerns about the safety of HDAC inhibitors in the context of COVID-19, given their potential to increase viral spread. The researchers emphasized the need for further research to fully comprehend the implications of these unexpected connections.
In conclusion, this study provides new insights into the complex relationship between cancer drugs, specifically HDAC inhibitors, and SARS-CoV-2 infection. The findings highlight the importance of caution when using HDAC inhibitors in the context of COVID-19 and underscore the need to understand the intricate interactions between viral infections and existing therapeutic interventions. Further research is crucial to fully grasp the implications of these unexpected connections. The study was published in the peer-reviewed journal Frontiers in Cellular and Infection Microbiology.