Background: The novel drug discovery of HIV- 1 integrase inhibitors is based on exploring
protein flexibility and QSAR studies using the protein structure. In this pursuit, several novel inhibitors
are under development. For example, Allosteric inhibitors (ALLINIs) and Multimerization integrase inhibitors
Objective: The objective is to discuss the development process of drug discovery and review the latest
developments in HIV-1 integrase inhibitors.
Method: A search of scientific literature and data on recent developments of HIV-1 integrase with an
intension of safe and effective drugs which inhibits the HIV-1 integrase. The information was organized
with an objective of giving Compressive developments leading to the discovery of integrase inhibitors
based on protein flexibility, simulation studies and QSAR.
Results: Identification of structural details and understanding the binding sites as lead to develop new
chemical entities which are promising integrase inhibitors. The role of protein flexibility in developing
novel inhibitors like ALLINIs and MINIs. For example Cabotegravir, Elvitegravir, Raltegravir and Dolutegravir.
Conclusion: Due to nonavailability of HIV-1 integrase in the crystalline form, we have to use the
approach of analogue crystal, for example, PFV integrase. Although there are a drastic difference in the
structural features in HIV-1 and PFV integrase. Researchers have to depend on PFV integrase for developing
HIV-1 integrase inhibitors by trial and error process.