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Influenza A virus (IAV) utilizes a specific set of proteins to facilitate its infectious cycle and evade host immune responses. Haemagglutinin (HA) is the primary surface glycoprotein that mediates viral binding to host sialic acid receptors and subsequent membrane fusion [1]. Neuraminidase (NA) is an essential enzyme that cleaves sialic acid residues, allowing the release of newly formed virions from the host cell surface [2]. The Matrix-2 (M2) protein acts as a proton-selective ion channel required for viral uncoating during entry and for maintaining pH balance during the assembly of new particles [3]. Nucleoprotein (NP) is a multifunctional protein that encapsidates the viral RNA segments, forming the ribonucleoprotein complexes necessary for viral transcription and replication [4]. These proteins are critical therapeutic targets; for example, neuraminidase inhibitors like oseltamivir are standard treatments to limit viral spread, while M2 inhibitors like amantadine were historically used to block viral uncoating [5]. However, the high mutation rate of IAV leads to frequent antigenic drift and the rapid development of drug resistance, posing a continuous challenge for the efficacy of both vaccines and antiviral drugs [6].
Inhibition of viral neuraminidase to prevent progeny release; blockade of the M2 ion channel to prevent viral uncoating; inhibition of haemagglutinin-mediated membrane fusion; and disruption of nucleoprotein-mediated ribonucleoprotein assembly.
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