AMB Volume 42, Issue 2, 2026 Pages 211-223 https://doi.org/10.59393/amb26420205
Structural Basis of the Disoxaril Resistance and Dependence of Coxsackievirus B1 Mutants
Atanasov B., Galabov A.S.
Disoxaril (WIN) inhibits replication of a broad spectrum of entero- and rhinoviruses through bonding to the hydrophobic pocket within VP1 coat protein. Previously we established Coxsackievirus B1 (CVB1) disoxaril mutants, sensitive (CVB1/SOF), resistant (CVB1/RES) and dependent (CVB1/DEP), which phenotypic characteristics being done. Moreover, analysis of the VP1 gene sequences of CVB1 mutants established an amino acid sequence, highly different at 195-255 in CVB1/RES with two point mutations, M213H and F237L, in the ligand-binding pocket. 3D-alignment of CVA9 over CVB3/B1 allows explicit transferring of two WIN-ligand atomic coordinates into CVB1 “canyon”, site-1 and site-2. The second site is forbidden for ligand in CVB1/SOF. It generated more than 100 models and all of them were treated with ‘clashing analyses’ for side chain rotamers. CVB1/RES has mainly steric and less energetic nature. In CVB1/DEP occupation of site-1 is restricted but site-2 can be filled. WIN molecule in site-2 interacts with the neighboring VP2 protein and all capsomers become chained in the pentamer. This explains the finding that CVB1/DEP mutant needs WIN compound to provoke coating. Analysis of oligomer complexes in the tetramer capsoer resulted in presentation of the whole capsid structure.
Keywords: disoxaril, coxsackievirus B1 mutants
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