The discovery was initially funded by the Australian biotechnology company Biota and was part of Biotas ongoing program to develop antiviral agents through rational drug design. Its strategy relied on the availability of the structure of influenza neuraminidase by X-ray crystallography. It was also known, as far back as 1974, that 2-deoxy-2,3-didehydro-N-acetylneuraminic acid (DANA), a sialic acid analogue, is an inhibitor of neuraminidase.Computational chemistry techniques were used to probe the active site of the enzyme, in an attempt to design derivatives of DANA that would bind tightly to the amino acid residues of the catalytic site, so would be potent and specific inhibitors of the enzyme. The GRID software by Molecular Discovery was used to determine energetically favourable interactions between various functional groups and residues in the catalytic site canyon. This investigation showed a negatively charged zone occurs in the neuraminidase active site that aligns with the C4 hydroxyl group of DANA. This hydroxyl is, therefore, replaced with a positively charged amino group; the 4-amino DANA was shown to be 100 times better as an inhibitor than DANA, owing to the formation of a salt bridge with a conserved glutamic acid (119) in the active site. Glu 119 was also noticed to be at the bottom of a conserved pocket in the active site that is just big enough to accommodate the larger, but more basic guanidine functional group.
At the end of the eleventh century, with the collapse of Byzantine power after the Battle of Manzikert, Bitlis fell under the control of Togan Arslan, a subject of the Shah Arman (Also called Ahlatshah) dynasty based in Akhlat after brief Dilmachoglu rule. It was also ruled by Ayyubid (1207–1231), Khwarezm Shahs (shortly rule in 1230), Sultanate of Rûm (1231–1243) and Ilkhanate (1243–1335). Emirate
Bitlis was a Kurdish emirate from the 13th to the 19th century. Though often subordinate to a succession of larger powers that ruled the Van region, it always maintained a measure of independence. In the 14th century its emirs, the Kurdish Rusaki family, were vassals of the Karakoyunlu and the emirates territory also consisted of several smaller emirates: Ahlat, Mush, and Hinis. The emir of Bitlis submitted to Timur in 1394, but later helped the re-establishment of Karakoyunlu control in the region. After the collapse of the Karakoyunlu state, the Bitlis emirate disintegrated. However, in the 1470s it took the Aq Qoyunlu (White Sheep Turkomans) three successive sieges to capture Bitlis and in 1494/95 the Ruzaki recaptured the town. Armenians formed a large part of the citys population. A number of monasteries were permitted to be built by the Kurdish emirs and during the fifteenth century, Biltis flourished as a center for Armenian manuscript production. Bitlis was forced to accept a Persian governor during the invasion of the Safavid Shah Ismail, but sided with the Ottoman forces as they approached the region. Its emir, Sheref, later changed his allegiance to the Persians.