Clinical studies have identified a cytokine storm in the third stage of disease progression in critical ill patients with coronavirus disease 2019 (COVID-19). Hence, effectively suppressing the uncontrolled immune response of the host towards the invaded viruses in a cytokine storm is a critical step to prevent the deterioration of patient conditions and decrease the rate of mortality. Therapeutic monoclonal antibodies (mAbs) are found to be effective for the management of acute respiratory distress syndrome in patients with COVID-19. In this review, we compiled all therapeutic mAbs targeting cytokine storm, which are in clinical trials for its repurposing in the management of COVID-19. Compilation of clinical trial data indicated that therapeutic monoclonal antibodies targeting interleukins (IL-6, IL-1ra, IL-8, IL-1β, IL-17A, IL-33), interferon-gamma, tumor necrosis factor-alpha, P-selectin, connective tissue growth factor, plasma kallikrein, tumor necrosis factor superfamily 14, granulocyte macrophage colony stimulating factor, colony stimulating factor 1 receptor, C-C chemokine receptor type 5, cluster of differentiation 14 and 147, vascular endothelial growth factor, programmed cell death protein-1, Angiopoietin - 2, human factor XIIa, complementary protein 5, natural killer cell receptor G2A, human epidermal growth factor receptor 2, immunoglobulin-like transcript 7 receptor, complement component fragment 5a receptor and viral attachment to the human cell were under investigation for management of severely ill patients with COVID-19. Among these, about 65 clinical trials are targeting IL-6 inhibition as the most promising one and Tocilizumab, an IL-6 inhibitor is considered to be the potential candidate to treat cytokine storm associated with the COVID-19.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have evolved from glucose-lowering agents to transformative therapies across multiple organ systems. This comprehensive review synthesizes current evidence on the mechanisms, established applications, and emerging therapeutic frontiers of GLP-1 RAs. Methods: We conducted a systematic literature search of PubMed, Embase, Cochrane Library, and ClinicalTrials.gov from inception through May 2025, using controlled vocabulary and free-text terms related to GLP-1 RAs, their mechanisms, and clinical applications. Results: GLP-1 RAs demonstrate pleiotropic effects through fundamental cellular mechanisms, including enhanced mitochondrial function, anti-inflammatory actions, improved cellular quality control, and comprehensive metabolic regulation. Established applications demonstrate robust efficacy in diabetes management (HbA1c reductions of 1.5–2.0%), obesity treatment (weight loss of 7–24%), and cardiovascular protection (14–20% reduction in major adverse cardiovascular events, or MACE). Emerging applications span neurological disorders, dermatological conditions, respiratory diseases, and novel applications in addiction medicine and autoimmune disorders. Conclusions: GLP-1 RAs represent a paradigmatic shift toward multi-system therapeutic intervention, with expanding evidence supporting their role as comprehensive metabolic modulators.

Overexpression of the gonadotropin-releasing hormone receptor (GnRH-R) plays a vital role in the advancement of reproductive malignancies such as ovarian, endometrial, and prostate cancer. Peptidomimetic GnRH antagonists are a substantial therapeutic development, providing fast and reversible suppression of gonadotropins by directly blocking GnRH-R. Unlike typical GnRH agonists, these antagonists prevent the early hormonal flare, have a faster onset of action, and have a lower risk of cardiovascular problems. These characteristics qualify GnRH antagonists as revolutionary therapy for diseases such as advanced prostate cancer, endometriosis, uterine fibroids, and in vitro fertilization procedures. Key GnRH peptide antagonists authorized by the regulatory agencies include Cetrorelix, Ganirelix, Abarelix, Degarelix, and Teverelix. Assisted reproductive technologies (ART) are dominated by Cetrorelix and Ganirelix, while Degarelix and Abarelix have shown significant promise in treating advanced prostate cancer. Teverelix appears as a next-generation GnRH antagonist with an ideal mix of efficacy and safety, showing promise in a variety of reproductive and hormone-dependent illnesses. This review investigates the pharmacological role of GnRH in reproductive physiology and its consequences in disease, emphasizing structural advances in third- and fourth-generation GnRH antagonists. All GnRH peptide-based antagonists were analyzed in detail for formulation strategy, pharmacokinetics, effectiveness, and safety. This review also emphasizes GnRH antagonists’ clinical promise, providing insights into their evolution and the possibility for future research in developing safer, more effective treatments for complicated hormonal diseases.

Bevacizumab (Bvz) is the most preferred recombinant humanized monoclonal antibody in biosimilar development due to its prominence as a standard treatment in the oncology space. Therapeutic monoclonal antibodies are typically more complex and unlikely to produce a replica. As a result, regulatory agencies allow approval of biosimilars that differ structurally and functionally from their reference product, but these differences should not have any clinical significance. To identify these significant discrepancies, it is essential to perform a thorough characterization of critical product attributes both in real-time and after storage until the product's expiration. In the present study, two Bvz biosimilar brands (Bio-1 and Bio-2) marketed in India were evaluated and compared with the reference product Avastin® to assess their degree of similarity. A comprehensive physicochemical characterization of biosimilars and reference product was performed using orthogonal techniques including LC-ESI-QTOF, MALDI-TOF, FTIR-ATR, iCIEF, rCE, nrCE, UV280, and RP-HPLC. Furthermore, Bvz formulations under study were subjected to various stress conditions of thermal (elevated temperature 50 ± 2 °C), chemical (acidic pH 3.0 ± 0.2, neutral pH 7.0 ± 0.2, and basic pH 10.0 ± 0.2), and mechanical (agitation 200 rpm) for comparative stability evaluation. Any alteration in the secondary structure of the native protein was detected and quantified using far-UV circular dichroism (CD), indicating an average of 15% and 11% loss in native antiparallel β-sheet conformation respectively in Bio-1 and Bio-2 upon exposure to elevated temperature and high pH. Additionally, covalent or non-covalent aggregates formed as a function of elevated temperature and agitation were quantified using SEC-MALS.