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Viral endocytosis is a complex biological process, rather than a single molecular target, through which many animal viruses gain entry into host cells. This pathway involves the hijacking of cellular mechanisms such as clathrin-mediated endocytosis, caveolae-mediated endocytosis, and macropinocytosis to transport the viral genome into the cytoplasm [2, 7]. Once internalized, the virus typically utilizes the acidic environment of the endosome as a trigger for membrane fusion or pore formation, allowing it to escape into the cytosol and begin replication [1, 13]. Because this process relies on hundreds of host cellular proteins—including clathrin, dynamin, and various adaptors—it is considered an attractive area for broad-spectrum antiviral drug development [4, 12]. Drugs such as Chloroquine and Umifenovir target the acidification and fusion steps within this process, though the broad necessity of endocytosis for normal cellular homeostasis often leads to concerns regarding toxicity and lack of specificity [6, 11].
Inhibition of endosomal acidification, disruption of clathrin assembly, inhibition of dynamin GTPase activity, or blocking of PIKfyve-mediated endosomal trafficking.
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