Identification of Potential SARS-CoV-2 Main Protease and Spike Protein Inhibitors from the Genus Aloe: An In Silico Study for Drug Development

Abstract

Severe acute respiratory syndrome coronavirus (SARS-CoV-2) disease is a global rapidly spreading virus showing very high rates of complications and mortality. Till now, there is no effective specific treatment for the disease. <i>Aloe</i> is a rich source of isolated phytoconstituents that have an enormous range of biological activities. Since there are no available experimental techniques to examine these compounds for antiviral activity against SARS-CoV-2, we employed an in silico approach involving molecular docking, dynamics simulation, and binding free energy calculation using SARS-CoV-2 essential proteins as main protease and spike protein to identify lead compounds from <i>Aloe</i> that may help in novel drug discovery. Results retrieved from docking and molecular dynamics simulation suggested a number of promising inhibitors from <i>Aloe</i>. Root mean square deviation (RMSD) and root mean square fluctuation (RMSF) calculations indicated that compounds <b>132, 134</b>, and <b>159</b> were the best scoring compounds against main protease, while compounds <b>115, 120</b>, and <b>131</b> were the best scoring ones against spike glycoprotein. Compounds <b>120</b> and <b>131</b> were able to achieve significant stability and binding free energies during molecular dynamics simulation. In addition, the highest scoring compounds were investigated for their pharmacokinetic properties and drug-likeness. The <i>Aloe</i> compounds are promising active phytoconstituents for drug development for SARS-CoV-2.