Provided are anti-heparan sulfate peptides and methods that employ those peptides for the prevention or treatment of viral infections, including herpesviral infections such as α-herpesviral, β-herpesviral, and γ-herpesviral infections, which are exemplified by HSV-1. CMV, and HHV-8 viral infections, respectively. Peptides may comprise at least 10 amino acids of the amino acid sequences(SEQ ID NO: 2) XRXRXKXXRXRX, (SEQ ID NO: 8) XRXRXXKXRXRX, (SEQ ID NO: 4) XXRRRRXRRRXK, and/or (SEQ ID NO: 10) KXRRRXRRRRXX, wherein X represents any amino acid. In some embodiments, peptides comprise at least 10 amino acids of the sequence LRSRTKIIRIRH (SEQ ID NO: 1), HRIRIIKTRSRL (SEQ ID NO: 7), MPRRRRIRRRQK (SEQ ID NO: 3), and/or KQRRRIRRRRM (SEQ ID NO: 9). Peptides may be coupled to one or more therapeutic compound(s) to generate peptide-therapeutic compound conjugates, wherein the therapeutic compound may be one or more of a nucleoside analog, an oligosaccharide, and a small molecule.
