Docking Studies on Antiviral Drugs for SARS
Virupakshaiah Dbm, Chandrakanth Kelmani · 2007
The importance of Protein – Ligand binding in biological systems should not be underestimated. Protein – Ligand binding has an important role in the function of living organisms and is one method, which the cell uses to interact with the variety of molecules that comes in contact with it. Ligand is a molecule with a high level of specificity towards a particular type of proteins and is of prime importance in the cells functioning and survival. Severe acute respiratory syndrome or SARS is a respiratory disease in humans which is caused by the SARS coronavirus. The treatment of coronavirus-associated SARS has been evolving and so far there is no consensus on an optimal regimen. The mainstream therapeutic interventions for SARS involve broad-spectrum antibiotics and supportive care, as well as antiviral agents and immunomodulatory therapy. The Protein- Ligand interaction plays a significant role in structural based drug designing. Ligand is a molecule with a high level of specificity towards a particular type of proteins and is of prime importance in the cells functioning and survival. In the present work we have taken the receptor Angiotensin converting enzyme 2 and identified the drugs that are commonly used against SARS (Severe Acute Respiratory Syndrome). They are Lopinavir, Ritonavir, Ribavirin, and Oseltamivir. The receptor Angiotensin converting enzyme 2 (ACE2) was docked with above said drugs and the energy value obtained are as follows, Lopinavir (-292.3) , Ritonavir (-325.6), Oseltamivir (-229.1), Ribavirin (-208.8) .Depending on the least energy value we have chosen the best two drugs out of the four conventional drugs. We tried to improve the binding efficiency and steric compatibility of the two drugs namely Ritonavir and Lopinavir. Several modifications were made to the probable functional groups (phenylic, ketonic groups in case of Ritonavir and carboxylic groups in case of Lopinavir respectively) which were interacting with the receptor molecule. Analogs were prepared with using software Marvin Sketch and were docked using a docking software HEX against the same receptor the, energy value obtained are, Lopinavir analog 17 (-332.7), Ritonavir analog 12 (-330.8). From this we came to know that some of the modified drugs are better than the original drugs. Of these molecules Lopinavir analog (17), Ritonavir analog (12) are probable lead molecules than the rest of the drugs for SARS owing to their high-energy value. Further work can be carried out to improve the steric compatibility of the drug based upon the work done above for a more energy efficient binding of the drugs to the receptor.