Researchers at the Indian Institute of Technology, Madras claim to have found a novel way to make HIV/AIDS drugs more effective. The findings of their study, published in Biochemistry, the peer-review Journal of the American Chemical Society, say that introducing electrostatic interaction sites on potential drug molecules can enhance the efficacy of the antiviral drug against the HIV virus. The research was led by Prof. Sanjib Senapati, Department of Biotechnology, IIT Madras, along with research scholars Mohammed Ahsan and Chinmai Pindi.
"Current inhibitors (molecules that bind with the enzyme, thereby making it unavailable to the virus for growth and maturation) that target HIV-1 protease (HIVPR, an essential enzyme that is used by the AIDS virus for growth and maturation), 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," Prof. Senapati, says.
The Molecular Dynamics (MD) simulation studies conducted by IIT Madras researchers 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, they felt.
"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," Prof. Senapati said.
The researchers propose that drug design strategies should embrace both electrostatics and van der Waals interactions to complement the HIVPR active site architecture. Further, the team believes that such compounds will be effective against both wild-type and resistant HIV variants. According to them, it is a paradigm-shifting idea and will offer a whole new approach to the development of drugs for HIV-AIDS.
Prof. Chandra Verma, who has a Ph.D. from Bioinformatics Institute, A*STAR, Singapore, and is not involved in this IIT Madras Research, predicts a bright future for HIV drug development, with such knowledge base.
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.