Role of Structural Flexibility of HIV-1 Integrase in the Design of Potent Anti-HIV Drugs

Author(s): Vinuth Chikkamath, Anantha Naik Nagappa*.

Journal Name: Current Chemical Biology

Volume 12 , Issue 1 , 2018

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Graphical Abstract:


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 (MINIs).

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.

Keywords: HIV-1 integrase, PFV integrase, ALLINIs, MINIs, dolutegravir, cabotegravir, protein flexibility.

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Article Details

Year: 2018
Page: [40 - 52]
Pages: 13
DOI: 10.2174/2212796812666180529103809

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