Repurposing Anticancer Drugs Targeting the MAPK/ERK Signaling Pathway for the Treatment of Respiratory Virus Infections

Abstract

Respiratory virus infections remain a significant challenge to human health and the social economy. The symptoms range from mild rhinitis and nasal congestion to severe lower respiratory tract dysfunction and even mortality. The efficacy of therapeutic drugs targeting respiratory viruses varies, depending upon infection time and the drug resistance engendered by a high frequency of viral genome mutations, necessitating the development of new strategies. The MAPK/ERK pathway that was well delineated in the 1980s represents a classical signaling cascade, essential for cell proliferation, survival, and differentiation. Since this pathway is constitutively activated in many cancers by oncogenes, several drugs inhibiting Raf/MEK/ERK have been developed and currently used in anticancer treatment. Two decades ago, it was reported that viruses such as HIV and influenza viruses could exploit the host cellular MAPK/ERK pathway for their replication. Thus, it would be feasible to repurpose this category of the pathway inhibitors for the treatment of respiratory viral infections. The advantage is that the host genes are not easy to mutate such that the drug resistance rarely occurs during short-period treatment of viruses. Therefore, in this review we will summarize the research progress on the role of the MAPK/ERK pathway in respiratory virus amplification and discuss the potential of the pathway inhibitors (MEK inhibitors) in the treatment of respiratory viral infections.