Researchers at IIT Madras working on a more effective drug to treat HIV/AIDS

Researchers at the Indian Institute of Technology Madras are paving the way to tackle HIV/AIDS in a much more efficient way through the introduction of a more powerful drug. The research team through the use of molecular dynamics simulations has shown that the introduction of electrostatic interaction sites on potential drug molecules can increase the efficacy of the antiviral drug in a fight with the HIV virus.

Prof Sanjib Senapati, Department of Biotechnology, IIT Madras, along with his research scholars, Mohammed Ahsan and Chinmai Pindi have done the research. The prestigious peer-review Journal of the American Chemical Society – Biochemistry has off late published their creation.

The dire crisis for better drugs to fight against the drug-resistant HIV strains has insisted the researchers like Prof Senapati get into the molecular structure of the protease in order to identify the weak sites for better inhibitor development.

The drug developers work on the route of attacking the HIV – 1 protease (HIVPR), an important enzyme used by the AIDS virus in order to grow and develop. Drug designers aim at developing efficient inhibitors of the enzyme – inhibitors are the molecules that clasp with the enzyme to make it impossible for the virus to grow and mature.

Further elaborating on the research, Prof Senapati exclaimed, “Current inhibitors that target HIVPR make use of the weak forces of attraction called ‘van der Waal’s forces’ to attach themselves to the protease molecule. Given that these forces are weak, the efficacy of the drug is variable and the virus will soon become resistant to them”.

Recent useful data obtained from the use of analytical techniques such as neutron diffraction and NMR, on the molecular structure of the target HVPR enzyme, have goaded Prof Senapati to re-study the HVPR- inhibitor pattern of binding. Taking help of state-of-art computational techniques, his team has discovered vital data to be put into use for designing more efficacious drugs.

The IIT Madras Researchers have conducted the Molecular Dynamics (MD) simulation studies that hint at the presence of a strong and asymmetrical electric charge in the active site of the HIVPR. It can permanently deactivate/inhibit the enzyme if a drug molecule can be designed with a complementary charge so that it can bind itself tightly with this active site through electrostatic attraction.

Prof Senapati stated, “Current drugs lack this electrostatic complementarity. This must be investigated because it is well- known that electrostatic forces between molecules are much stronger than van der Waals forces”.

So, the team along with Prof Senapati is of the opinion that the drug design strategies should include both the electrostatic and van der Waals interactions in order to complement the HIVPR active site architecture. Moreover, the team opines that such compounds will effectively work against both the wild-type and HIV-resistant variants. In connection to HIV-AIDS, this paradigm–shifting idea shall offer a whole new approach in the development of drugs.

A Ph.D. from Bioinformatics Institute, A*STAR, Singapore, Prof Chandra Verma, who is not involved in this IIT Madras Research, sees a glorious future for HIV drug development.

Commenting on Prof Senapati’s work, Prof Verma comments, “This is a remarkable discovery and one that will hopefully open a new window into novel screening/designing efforts that will lead to the availability of drugs that can combat both the wild type and the resistant protease, satisfying to an unmet need in the arsenal of drugs used to treat the disease”.