*3.4. The AstraZeneca India (AZI) E*ff*ort*

**Gyrase as a target:** One of the favorite targets for anti-TB drug discovery is the 'gyrase enzyme'. This is because of the multiple steps involved in the mechanistic of the 'negative supercoiling' enzyme reaction, several steps of which have been shown to be inhibitable [43]. Additionally, the availability of the several crystal structures of the enzyme has also helped in developing diverse screening approaches, as well as in building SAR of the identified inhibitors.

AZI employed multiple 'hit' generation approaches like high-throughput screening (HTS) of the AZ library, fragment library screening, targeted library screening, and pharmacophore-based screening, as well as virtual screening, in the quest for robust novel inhibitors. Shirude and Hameed [44] reviewed the features of the diverse set of inhibitors identified by the different groups. Several novel chemical entities were identified and are being investigated further (Table 1).



The key learning from these extensive efforts on 'revisiting gyrase as an established target' are as follows:

