Broad-spectrum host-targeting antivirals for rhinovirus infections: mechanisms and future perspectives

Figures

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  Figure 1. Rhinovirus genomic structure. Rhinovirus belongs to the single-stranded positive-sense RNA viruses, with a total length of approximately 7,200 bp. The capsid protein VP1 is primarily responsible for receptor recognition; VP4, VP2, VP3, and VP1 are processed to form the rhinovirus capsid, while the remaining proteins are processed to generate proteases, VPg and RNA-dependent RNA polymerase (RdRP).

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  Figure 2. Future strategies against viral infection. The schematic diagram was created using BioRender.com.

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  Figure 3. Antiviral strategies targeting key steps in the replication cycle of rhinovirus. RRMA and 14C11 block viral entry by targeting cellular ICAM-1. Cilomilast and EPs 7630 downregulate ICAM-1 expression to hinder viral attachment. Tremacamra and recombinant soluble LDLR fragments function as decoy receptors to intercept viruses and prevent entry. 4H30 targets LDLR, and HEX17 interacts with both ICAM-1 and LDLR to suppress viral entry. Niclosamide and P9R inhibit endosomal acidification, thereby blocking viral uncoating and genomic RNA release. Itraconazole, 25OHC, and 27OHC interact with OSBP to suppress viral replication. TVB-3166 inhibits viral protein synthesis. Simvastatin alleviates virus-triggered inflammatory responses via suppressing STAT1 phosphorylation in the JAK/STAT pathway. Silvestrol impedes the assembly of translation initiation complexes to exert antiviral effects. Enviroxime-like compounds, LY294002 and 2-DG, restrain viral replication by inhibiting PI4KIIIβ, blocking Akt phosphorylation, and suppressing glycolysis, respectively. YVAD relieves virus-induced inflammation through inhibiting excessive activation of the RIG-I inflammasome pathway. These antiviral drugs…