2D QSAR APPROACH TO DEVELOP NEWER GENERATION SMALL MOLECULES ACTIVE AGAINST SARS-COVIDAbstract
We are in the half past of 2022, but still, we are facing the coronavirus pandemic situation. When a patient is hospitalized, only some FDA-approved drugs were administered to cure the patient. In treating coronavirus infection, nitazoxanide, granulocyte-macrophage colony-stimulating factor inhibitors, and various monoclonal antibodies are present. But all the molecules used in the treatment were not so effective in fully curing the patient. So, to break this jinx to develop of newer generation anti-SARS-CoV-2 drug molecules, computational approaches played an essential role. 2D QSAR studies related to anti-SARS-CoV-2 molecule development, some QSAR models observed with good statistical parameters such as R2: 0.748, cross-validated Q2 (LOO): 0.628, external predicted R2: 0.723 and another model suggested with R2: 0.764, Q2: 0.627 and Rm2: 0.610, Q2 (F1): 0.727, Q2 (F1): 0.652, MAE score: 0.127. We developed a new 2D QSAR model with a higher number of molecules and greater statistical parameters. A dataset of 84 anti-SARS-CoV2 molecules was obtained from literature followed by descriptor calculation PADEL software; the QSAR model was generated using the Modelability index, dataset pretreatment, division, MLR equation, validation, and Y randomization test. The model was pIC50 = -1.79268(+/-0.3652) +0.07995(+/-0.03551) naaaC -0.4051(+/-0.09672) nsssN -0.45945(+/-0.11025) SHsOH +1.23189(+/-0.28144) ETA_BetaP with R2 and Q2 values were 0.87028 and 0.70493 with MAE fitness score value: 0.14298. Atoms E-state and electronic features of the molecules directly related to anti-SARS-CoV-2 drug activity. It can be easily concluded that we want to develop a small molecule effective against SARS-CoV-2 disease in the near future.
Supriyo Saha * and Dilip Kumar Pal
School of Pharmaceutical Sciences & Technology, Sardar Bhagwan Singh University, Dehradun, Uttarakhand, India.
15 July 2022
19 August 2022
01 September 2022
01 March 2023