Historical Approaches to Treating Influenza Influenza, commonly known as the flu, has circulated among humans for centuries. Despite its enduring presence, effective treatments for influenza have been elusive until recently. For much of the 20th century, bed rest and supportive care were the primary treatment options available to patients suffering from the flu. While most influenza infections resolve on their own within a week to ten days, severe cases can lead to hospitalization or even death. With limited therapeutic options, past influenza pandemics like the 1918 Spanish Flu pandemic resulted in tens of millions of fatalities worldwide. The development of antiviral drugs in the mid-20th century marked the first major advance in influenza therapeutics. Two classes of antiviral drugs in particular have become mainstays of flu treatment – adamantanes and neuraminidase inhibitors. Adamantanes like amantadine and rimantadine target the M2 protein of influenza A viruses to inhibit viral uncoating inside host cells. However, widespread resistance to adamantanes emerged in influenza A(H3N2) and influenza A(H1N1) strains in the 1990s and 2000s. Neuraminidase inhibitors oseltamivir and zanamivir became the standard of care as they target the neuraminidase protein found on both influenza A and B viruses to prevent viral spread. While neuraminidase inhibitors remain effective against most seasonal flu strains, some resistant viruses have also emerged in recent years. New Antiviral Strategies Target Host Factors With viral resistance posing an ongoing challenge, researchers have increasingly focused efforts on developing antivirals that target host processes critical for viral replication instead of viral proteins directly. Host-directed Influenza Therapeutics strategies aim to limit opportunities for resistance by making it difficult for viruses to adapt. Several promising host-targeting antiviral candidates for influenza are now advancing through clinical trials. One host factor under investigation is sphingosine kinase 2 (SPHK2), an enzyme that generates the lipid signaling molecule sphingosine-1-phosphate (S1P) when activated. SPHK2 activity is induced upon influenza virus infection and appears necessary for efficient viral replication. In a phase 1 clinical trial, the first-in-class SPHK2 inhibitor ABC294640 was found to be well-tolerated in healthy volunteers and demonstrated significant reductions in viral load when administered to patients with symptomatic influenza. Oloni Pharmaceuticals is now conducting phase 2 trials of ABC294640 to further evaluate safety and efficacy. Another antiviral approach focuses on blocking histone deacetylases (HDACs), epigenetic regulators that influenza viruses hijack to reprogram the host cell environment. RG6016 is a pan-HDAC inhibitor under development by Hoffmann-La Roche that prevents this epigenetic remodeling. Phase 1 and 2 trials have shown RG6016 to be safe and well-tolerated in healthy individuals and influenza patients. Efficacy results from a recent phase 2b study indicate that early treatment with RG6016 may significantly reduce symptom severity and viral shedding compared to placebo. Roche is continuing phase 3 trials to support licensure. Progress Towards Broadly Protective Therapeutics In parallel with traditional antiviral drug development, scientists are also engineering therapies with the goal of achieving broad protection against multiple influenza strains, including pandemic variants. Such universal influenza treatments could minimize the need to update vaccines and antivirals each season as new viral strains circulate. One universal flu therapeutic approach aims to elicit immunity against highly conserved stalk regions on the viral hemagglutinin (HA) protein rather than the more variable globular head domain targeted by natural infection and vaccines. Antibodies that recognize the HA stalk have potential for broader protective ability. Researchers at IGM Biosciences have developed IgM antibodies that exclusively target the HA stalk. In animal studies, these IgM antibodies provided protection against divergent influenza A strains when administered as a post-exposure prophylactic or treatment. IGM is now preparing to initiate first-in-human clinical trials. Other groups are engineering antibodies, immune cells, and vaccines programmed to target internal influenza proteins like the matrix protein 2 or nucleoprotein that exhibit less antigenic drift than surface glycoproteins. For example, researchers demonstrated that chimeric antigen receptor (CAR) T cells genetically modified to recognize the influenza matrix protein 2 protected mice from lethal challenge with different influenza A subtypes. Get this Report in Japanese Language- インフルエンザ治療薬
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Alice Mutum is a seasoned senior content editor at Coherent Market Insights, leveraging extensive expertise gained from her previous role as a content writer. With seven years in content development, Alice masterfully employs SEO best practices and cutting-edge digital marketing strategies to craft high-ranking, impactful content. As an editor, she meticulously ensures flawless grammar and punctuation, precise data accuracy, and perfect alignment with audience needs in every research report. Alice's dedication to excellence and her strategic approach to content make her an invaluable asset in the world of market insights.
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