Abstract
With the anti-HIV vaccines still not available, development of other ways to prevent the spread of AIDS must be given very high priority. Targeting the envelope proteins of the virus with the aim of preventing membrane fusion and cell entry has been validated for disrupting viral spread, but is not yet practical in the clinic. We have been studying a number of antibodies targeting the viral protein gp41 and their complexes with a five-helix-bundle mimic of this protein. Although several tightly binding antibodies have been produced, only some of them are capable of neutralizing the virus, whereas others are not.
Structural studies of their complexes have given us clues to these discrepancies. We have been also investigating a number of lectins with strong antiviral properties that are being developed as components of female-controlled virucides. These lectins bind to the high-mannose carbohydrates attached to gp120. Extensive engineering of griffithsin resulted in a monomeric form of this lectin which, although still capable of binding complex carbohydrates very tightly, lost its antiviral properties. Structural studies of griffithsin and its carbohydrate complexes elucidated the mode of its antiviral activity and should help in further development of this and other lectins as antiviral agents.
