Docking assay of small molecule antivirals to p7 of HCV

•Binding poses of antivirals to monomers and hexameric bundles of p7 of HCV.•Guanidine based ligands bind better than derivatives of adamantanes and iminosugars.•Binding of the best candidates is at the site of the loop.•Hydrogen bonding and hydrophobic interactions are important.

Protein p7 of HCV is a 63 amino acid channel forming membrane protein essential for the progression of viral infection. With this momentousness, p7 emerges as an important target for antiviral therapy. A series of small molecule drugs, such as amantadine, rimantadine, amiloride, hexamethylene amiloride, NN-DNJ and BIT225 have been found to affect the channel activity. These compounds are docked against monomeric and hexameric structures of p7 taken at various time steps from a molecular dynamics simulation of the protein embedded in a hydrated lipid bilayer. The energetics of binding identifies the guanidine based ligands as the most potent ligands. The adamantanes and NN-DNJ show weaker binding energies. The lowest energy poses are those at the site of the loop region for the monomer and hexamer. For the latter, the poses show a tendency of the ligand to face the lumen of the pore. The mode of binding is that of a balance between hydrophobic interactions and hydrogen bond formation with backbone atoms of the protein.

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