A method of inhibiting a viral infection of a host comprising administering to the host an anti-viral griffithsin polypeptide comprising SEQ ID NO: 3 or a fragment thereof comprising at least eight contiguous amino acids, a nucleic acid encoding the anti-viral polypeptide, or an antibody to the anti-viral polypeptide. A method of inhibiting a virus in a sample comprising contacting the sample with an anti-viral griffithsin polypeptide or antibody thereto also is provided.