To maximize the efficiency of photo-cross-linking, two residues (leu 11 and phe 14 ) in a region (aa 9-15) known to be critical for viral infection (Schulze et al., 2010) were chosen for substitution with L-photoleucine. Leu 11 is 100% conserved among HBV genotypes, and the 14th residue is a phenylalanine in most genotypes but a leucine in some HBV strains of genotypes F and G. Changing phe 14 to leucine (F14L) did not significantly affect the binding of HDV virion to primary Tupaia hepatocytes (PTHs) ( Figure 1B) . The activity of the synthesized peptide ligand Myr-47/WT b (or WT b hereafter) containing photo-leucines at positions 11 and 14 was also confirmed ( Figure 1C,D) . WT b inhibited HDV binding to PTHs with efficiency comparable to Myr-47/WT that is comprised of all natural amino acids ( Figure 1A,C) . A peptide Myr-47/N9K b (or N9K b hereafter) similar to WT b but with an additional mutation at the ninth residue (N9K) did not block HDV binding to PTHs ( Figure 1C ). WT b but not N9K b inhibited viral infection of HBV and HDV on PTHs ( Figure 1D ). Both WT b and N9K b peptides were myristoylated at the N-terminus and conjugated with a biotin tag on a C-terminal lysine residue ( Figure 1A ). N9K b differs from WT b by only one amino acid but completely lost these blocking activities. Thus, N9K b was used as a negative control for WT b . In addition, a monoclonal antibody (mAb) 2D3, which specifically recognizes an epitope adjacent to the critical receptor-binding region of the peptides and shared by both WT b and N9K b , was developed ( Figure 1E ).