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. 2021 Aug 7;10(8):2022. doi: 10.3390/cells10082022

Figure 4.

Figure 4

Interactions between MERS-CoV and autophagy. MERS-CoV induces autophagosome formation by NSP4 and blocks autophagosome–lysosome fusion by NSP6, p4b, and p5. The latter is accomplished via (yellow circles): (1) increased phosphorylation of SKP2, (2) enhanced polyubiquitination and (3) degradation of BECN1, (4) decreased ATG14 oligomerization, (5) reduced interaction of the autophagosomal SNARE, STX17, with the lysosomal SNARE, VAMP8, via the bridging protein SNAP29, leading to (6) reduced autophagosome–lysosome fusion and accumulation of autophagosomes and MERS-CoV virions. Inhibition of SKP2 with SMIP004 reverses these effects of MERS-CoV and decreases viral load. The same can be accomplished via other BECN1 preservation strategies, such as inhibition of the GLIPR2–BECN1 interaction with Tat-B or disruption of the BCL2-BECN1 binding with ABT-737. Protein and inhibitor symbols are in bold. Human proteins are in ovals. Inhibitor symbols are underlined. P, phosphate; Ub, ubiquitin.