Introduction
respiratory infections, tumor necrosis, TNF-α, viral infection, coronavirus disease 2019
RESPIRATORY INFECTIONS, VIRUS, CORONAVIRUS DISEASE 2019, SARS-COV-2 INFECTION, TUMOR NECROSIS, VIRAL INFECTION, ADHESION, CORONAVIRUS, SEVERE ACUTE RESPIRATORY SYNDROME, VIRAL RESPIRATORY INFECTION, INFLUENZA
Since the initial detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in December 2019 in Wuhan, China, the rapid transmission of novel coronavirus disease 2019 (COVID-19) has prompted investigations into various drugs for treating this viral respiratory infection. Despite extensive efforts, a safe and effective treatment for COVID-19 remains elusive. This underscores the need for alternative therapeutic agents targeting SARS-CoV-2 infection. Two promising candidates originating from the Notably, both GA and 18β exhibit antiviral properties against SARS-CoV-2, employing distinct mechanisms to hinder viral entry and replication within cells (GA and 18β exhibit anti-inflammatory and immune response effects through the modulation of cytokines, including interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), interleukins (IL) such as IL-17, IL-1β, IL-4, IL-5, IL-6, IL-8, IL-10, and IL-12. Additionally, they affect intercellular adhesion molecules and transcription factors. This cytokine-mediated modulation may occur through different mechanisms, such as reducing the activity of the inflammatory mediator toll-like receptor (TLR), preventing virus binding to the ACE2 receptor (Of particular interest, IL-17, a pro-inflammatory cytokine, has been observed at elevated levels in the peripheral blood of SARS-CoV-2 infected patients. This cytokine can trigger various inflammatory cytokines, including IL-6, IL-1β, IL-1, and IL-8 (The anti-inflammatory activity of GA and 18β has also been demonstrated in the context of respiratory infections caused by other viruses, such as influenza and respiratory syncytial virus (Both GA and 18β possess therapeutic and pharmacological attributes, including non-cytotoxicity, non-carcinogenicity, and a safe dosage range (Notably, both compounds are components of herbal formulations containing GA and 18β (as Furthermore, the mechanism of action of GA and 18β against the SARS-CoV-2 virus in humans remains inadequately understood, and their administration via nebulization has not been extensively explored. Inhalation-based drug delivery presents a promising avenue to address a key challenge associated with hydrophobic molecules like 18β, enhancing solubility and permeability for improved bioavailability while achieving high local concentrations in the respiratory system to combat viral infection without inducing side effects (