The pressing need for better drugs to combat drug-resistant HIV strains led researchers to delve into molecular structure of protease to identify weak sites that can offer a handle for better inhibitor development
Researchers at the Indian Institute of Technology, Madras, are working on a revolutionary new idea that can pave the way to effective drugs for treating HIV/AIDS. Researchers are using molecular dynamics simulations. They have shown that introducing electrostatic interaction sites on potential drug molecules can enhance the efficacy of the antiviral drug against the HIV virus.
AIDS is one of the most devastating diseases and is a major cause of death among youth in many parts of the world.
Since its outbreak nearly four decades ago, tremendous efforts have been directed towards development of antiretroviral therapies that target different stages in the life cycle of the virus that causes this deadly disease.
The study was led by Professor Sanjib Senapati, Department of Biotechnology, IIT Madras. The findings were published in the Journal of the American Chemical Society – Biochemistry.
Sanjib said that the pressing need for better drugs to combat drug-resistant HIV strains led the team to delve into the molecular structure of the protease to identify weak sites that can offer a handle for better inhibitor development.
Recent useful data obtained using analytical techniques such as neutron diffraction and NMR, on the molecular structure of the target HVPR enzyme, have encouraged Prof. Sanjib Senapati to re-visit the patterns of HVPR-inhibitor binding. By using state-of-art computational techniques his team has uncovered vital data that can be used for design of more efficacious drugs.
The study showed the presence of a strong and asymmetrical electric charge in the active site of the HIVPR. If a drug molecule can be designed with a complementary charge, so that it can bind tightly with this active site through electrostatic attraction, it can permanently deactivate/inhibit the enzyme.
Sanjib said that current drugs lack electrostatic complementarity. This must be investigated because it is well-known that electrostatic forces between molecules are much stronger than van der Waals forces.
IIT Madras researchers proposed that drug design strategies should embrace both electrostatics and van der Waals interactions to complement the HIVPR active site architecture.
The team said that such compounds will be effective against both wild type and resistant HIV variants.