Viral Mechanisms and Drug Influences on Janus Kinase/Signal Transducers and Activators of Transcription (JAK/STAT) Pathway in Human Coronaviruses Infection: A Systematic Review

Abstract

Background and Aim: Janus kinases/signal transducers and activators of transcription (JAK/STAT) pathway is crucial for various stages of immunity, from innate to adaptive responses. Type 1 IFNs activate JAK/STAT pathway by binding to receptors on JAK, phosphorylating STAT and upregulating interferon-stimulated genes (ISGs) leading to cytokines production. Viruses, however, have developed mechanisms to prevent antiviral type I IFNs induction, resulting in active viral replication. This study seeks to review viral mechanisms, drug influences, and vitamin D supplements affecting the JAK/STAT pathway in human coronavirus infection. Methods: Literature searches were conducted across Google Scholar, Scopus, PubMed, and ScienceDirect in accordance with the PRISMA guidelines. The study included all publications that satisfied the PRISMA criteria, were written in English, and fell within a 10-year window from July 2014 to June 2024. Forty-seven (47) studies satisfied the requirement for selection, out of which 31 studies were on viral mechanism, 12 were on drug interaction, and 2 were on vitamin D supplements. Results: There is consistent evidence of viral proteins, including ORF6, ORF8, spike, NSP14, NSP 1, and N of human coronaviruses disrupting the JAK/STAT pathway. Ruxolitinib, baricitinib, and Liantua Qingwen capsules have, however, been shown to stabilize the pathway by attacking viral proteins, inhibiting some pro-inflammatory cytokines, and downregulating STAT components to lessen cytokine storm, during hyperinflammation. Conclusion: This finding emphasizes the need for controlled regulation of JAK/STAT pathway to address coronavirus infections and immune disruptions, with continued research essential in developing targeted treatment against present and future viral threats.