2-deoxy-D-glucose for COVID-19

ABSTRACT Background and Aim Post‐acute sequelae of SARS‐CoV‐2 infection (PASC), commonly referred to as long COVID, has emerged as a significant global health concern, marked by persistent symptoms and chronic inflammation following recovery from acute COVID‐19. A central driver of PASC pathogenesis is the sustained cytokine storm—an exaggerated and prolonged pro‐inflammatory response that leads to ongoing tissue injury and multisystem dysfunction. This review aims to synthesize current knowledge on cytokine dysregulation in PASC and evaluate emerging therapeutic strategies targeting these immunopathological mechanisms. Methods A narrative review methodology was employed, drawing from recent peer‐reviewed publications, clinical trial databases, and immunological studies published between 2020 and 2025. Articles focusing on cytokine profiles in PASC, immune reprogramming, and immunomodulatory therapies were included. Mechanistic studies, biomarker research, and translational trials involving corticosteroids, cytokine inhibitors, Janus kinase (JAK) inhibitors, and novel biologics were critically analyzed. Results The literature reveals that elevated levels of IL‐6, IL‐1β, TNF‐α, and IFN‐γ persist in a subset of PASC patients, contributing to chronic systemic and organ‐specific inflammation. Emerging therapies—including IL‐6 and IL‐1 receptor antagonists, JAK inhibitors, and CNS‐penetrant anti‐inflammatory agents—demonstrate promise in modulating cytokine storms and improving clinical outcomes. Recent insights into cytokine profiling, trained immunity, and neuroimmune crosstalk suggest potential for precision‐based interventions tailored to distinct inflammatory phenotypes in PASC. Conclusion Persistent cytokine dysregulation underlies the pathophysiology of PASC and offers actionable targets for therapeutic intervention. Immunomodulatory strategies, when guided by biomarker profiling and systems biology approaches, hold promise for mitigating long‐term complications of COVID‐19. Future research should prioritize personalized treatment algorithms to address the heterogeneity of PASC and enhance patient recovery.

RNA viruses, such as SARS-CoV-2 and influenza, pose a persistent threat to global public health. Their high mutation rates undermine the effectiveness of conventional direct-acting antivirals (DAAs) and facilitate drug resistance. As obligate intracellular parasites, RNA viruses rely extensively on host cellular machinery and metabolic pathways throughout their life cycle. This dependency has prompted a strategic shift in antiviral research—from targeting the mutable virus to targeting relatively conserved host dependency factors (HDFs). In this review, we systematically analyze how RNA viruses exploit HDFs at each stage of infection: utilizing host receptors for entry; remodeling endomembrane systems to establish replication organelles; hijacking transcriptional, translational, and metabolic systems for genome replication and protein synthesis; and co-opting trafficking and budding machinery for assembly and egress. By comparing strategies across diverse RNA viruses, we highlight the broad-spectrum potential of HDF-targeting approaches, which offer a higher genetic barrier to resistance, providing a rational framework for developing host-targeting antiviral therapies.

Since the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its resultant pneumonia in December 2019, the cumulative number of infected people worldwide has exceeded 670 million, with over 6.8 million deaths. Despite the marketing of multiple series of vaccines and the implementation of strict prevention and control measures in many countries, the spread and prevalence of SARS-CoV-2 have not been completely and effectively controlled. The latest research shows that in addition to angiotensin converting enzyme II (ACE2), dozens of protein molecules, including AXL, can act as host receptors for SARS-CoV-2 infecting human cells, and virus mutation and immune evasion never seem to stop. To sum up, this review summarizes and organizes the latest relevant literature, comprehensively reviews the genome characteristics of SARS-CoV-2 as well as receptor-based pathogenesis (including ACE2 and other new receptors), mutation and immune evasion, vaccine development and other aspects, and proposes a series of prevention and treatment opinions. It is expected to provide a theoretical basis for an in-depth understanding of the pathogenic mechanism of SARS-CoV-2 along with a research basis and new ideas for the diagnosis and classification, of COVID-19-related disease and for drug and vaccine research and development.

The COVID-19 pandemic has flared across every part of the globe and affected populations from different age groups differently. People aged from 40 to 80 years or older are at an increased risk of morbidity and mortality due to COVID-19. Therefore, there is an urgent requirement to develop therapeutics to decrease the risk of the disease in the aged population. Over the last few years, several prodrugs have demonstrated significant anti-SARS-CoV-2 effects in in vitro assays, animal models, and medical practice. Prodrugs are used to enhance drug delivery by improving pharmacokinetic parameters, decreasing toxicity, and attaining site specificity. This article discusses recently explored prodrugs such as remdesivir, molnupiravir, favipiravir, and 2-deoxy-D-glucose (2-DG) and their implications in the aged population, as well as investigating recent clinical trials.