Foscarnet (phosphonoformate trisodium salt), an antiviral used for the treatment 
of HIV and herpes virus infections, also acts as an activator or inhibitor of 
the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1). Interaction of the drug 
with 11 CA isozymes has been investigated kinetically, and the X-ray structure 
of its adduct with isoform I (hCA I-foscarnet complex) has been resolved. The 
first CA inhibitor possessing a phosphonate zinc-binding group is thus 
evidenced, together with the factors governing recognition of such small 
molecules by a metalloenzyme active site. Foscarnet is also a clear-cut example 
of modulator of an enzyme activity which can act either as an activator or 
inhibitor of a CA isozyme.