Current Drug Targets - Volume 26, Issue 8, 2025

Rheumatoid arthritis is a chronic autoimmune condition marked by persistent inflammation and joint deterioration, affecting millions of people worldwide. The objective of many of the drugs being prescribed for treating RA patients is to reduce inflammation and halt the progression of the disease. Additionally, several of these therapeutic options have disadvantages, namely the potential for illness recurrence and unfavorable side effects with prolonged usage. Due to these inefficiencies, treating RA now requires an entirely novel approach. In recent times, there has been a shift in emphasis towards directly targeting transcription factors (TFs) due to their crucial involvement in the progression of RA, triggering essential pro-inflammatory adhesion molecules, enzymes, chemokines, and cytokines. Considering this, researchers are investigating synthetic and natural compounds as potential options to target essential TFs and associated signaling pathways. This review focuses on the potential natural compounds and synthetic drugs to target four significant TFs, namely, hypoxia-inducible factor 1α, nuclear factor erythroid 2-related factor 2, retinoic acid-related orphan receptor gamma t, and signal transducer and activator and transcription, highlighting their contributions to revolutionizing RA treatment, thus aiming for more effective and safer therapeutic options. This review also offers an overview of the current status of various natural compounds and synthetic drugs under consideration for targeting the signaling pathways that trigger the activation of TFs.

Globally, high mortality is brought on by RNA viruses, which are linked to chronic human disorders. Viruses dominate the WHO's current ranking of the top 10 global health hazards, especially RNA viruses. RNA viruses, like HIV, SARS-CoV-2, and influenza, which are among the most prevalent and frequently encountered RNA viruses, use RNA as their genetic material, making them prone to quick changes. They adapt rapidly, complicating the body's immune responses. HIV, a significant retrovirus, infiltrates the immune system, causing AIDS by compromising defenses against infections. SARS-CoV-2, which led to COVID-19, sparked a worldwide pandemic with respiratory symptoms, emphasizing the need for research and therapeutic innovations. The COVID-19 pandemic has demonstrated the insufficiency of available resources in effectively addressing emerging viral infections. Influenza, a seasonal RNA virus, triggers flu outbreaks, impacting public health. Research is crucial to understanding how these viruses interact with hosts, aiding the development of effective treatments and strengthening our ability to face new viral threats. The most effective defenses against viral illnesses are virus-specific vaccinations and antiviral drugs. The present review emphasizes the prevalence of the three most pathogenic and widespread RNA viruses, namely HIV, influenza, and SARS-CoV2, their pathophysiology, and the current treatment with FDA-approved drugs. It also incorporates novel analogs that are under clinical trials as there is an urgent need for innovative antiviral medications, and enormous global efforts are required to find secure and efficient cures for these viral infections.

Several fibroblast growth factors are expressed in the developmental stage, while others are present in adults. They are vital in maintaining cellular homeostasis and signaling important cellular functions, such as regeneration and growth. Over the years, a spike of interest has been observed in clinical applications of the different members of this family, especially for their implications in glucose and lipid homeostasis, cancer, and regeneration. Yet, the extent of this vast family's roles in different cellular activities and their mechanism of action remain unclear. Furthermore, they are structurally unstable molecules, making clinical applications more difficult. This work reviews the mechanism of action of FGFs and offers valuable insights into their therapeutic potential.