Abstract
RNA viruses always have been a serious concern for human health by causing several outbreaks, often pandemics. The excessive mortality and deaths associated with the outbreaks caused by these viruses were due to the excessive induction of pro-inflammatory cytokines leading to cytokine storm. Cytokines are important for cell-to-cell communication to maintain cell homeostasis. Disturbances of this homeostasis can lead to intricate chain reactions resulting in a massive release of cytokines. This could lead to a severe self-reinforcement of several feedback processes, which could eventually cause systemic harm, multiple organ failure, or death. Multiple inflammation-associated pathways were involved in the cytokine production and its regulation. Different RNA viruses induce these pathways through the interplay with their viral factors and host proteins and miRNAs regulating these pathways. This review will discuss the interplay of host proteins and miRNAs that can play an important role in the regulation of cytokine storm and the possible therapeutic potential of these molecules for the treatment and the challenges associated with the clinical translation.