The COVID-19 pandemic has underscored the need for effective and affordable antiviral drugs. Anthropogenic activities have increased interactions among humans, animals, and wildlife, contributing to the emergence of new and re-emerging viral diseases. RNA viruses pose significant challenges due to their rapid mutation rates, high transmissibility, and ability to adapt to host immune responses and antiviral treatments. The World Health Organization has identified several diseases (COVID-19, Ebola, Marburg, Zika, and others), all caused by RNA viruses, designated as being of priority concern as potential causes of future pandemics. Despite advances in antiviral treatments, many viruses lack specific therapeutic options, and more importantly, there is a paucity of broad-spectrum antiviral drugs. Additionally, the high costs of current treatments such as Remdesivir and Paxlovid highlight the need for more affordable antiviral drugs. Cyclic peptides from natural sources or designed through molecular modeling have shown promise as antiviral drugs with stability, low toxicity, high target specificity, and low antiviral resistance properties. This review emphasizes the urgent need to develop specific and broad-spectrum antiviral drugs and highlights cyclic peptides as a sustainable solution to combat future pandemics. Further research into these compounds could provide a new weapon to combat RNA viruses and address the gaps in current antiviral drug development.

Metabolic dysfunction–associated steatotic liver disease (MASLD) constitutes a primary cause of hepatocellular carcinoma (HCC). However, the transcriptional programs linking disease progression to tumor biology remain incompletely defined. Here, we aimed to identify conserved transcriptional programs underlying MASLD progression and to determine their biological organization, cellular context, and relevance in hepatocellular carcinoma. To accomplish this, we used an integrative analytical scheme across independent cohorts, including bulk liver transcriptomic datasets spanning disease stages (n = 63 and n = 170), clinical validation in the TCGA-LIHC cohort (n = 423), single-cell transcriptomic mapping, and external validation. Through this approach, we identified a coordinated immunometabolism transcriptional program associated with disease progression, encompassing 2,255 genes and enriched for metabolic and immune signaling pathways. Furthermore, immune profiling revealed structured remodeling, characterized by attenuation of global immune activity and redistribution of immune cell populations across disease stages. Network analysis uncovered a densely interconnected transcriptional module with central hub genes, denoting a coordinated regulatory architecture. Finally, cross-cohort validation identified a conserved core set of twenty-two genes that were reproducibly associated with disease progression. This program was preserved across independent datasets and persisted in hepatocellular carcinoma. Furthermore, it exhibited heterogeneous activation and modest prognostic value. In addition, single-cell analysis localized transcriptional activity to hepatocytes, endothelial cells, and macrophages, thereby defining a multicellular axis underlying disease progression. Collectively, these findings demonstrate that MASLD progression is a conserved immunometabolic transcriptional program that spans disease stages and malignancy.