Theses (MSc. Molecular Medicine)

Around December 2019, news reports of a mysterious pneumonia-like disease started making headlines. Later discovered to be a novel SARS-CoV-2 virus, the world was woefully underprepared for its aggressiveness. Since the World Health Organization declared a global pandemic in March 2020, the virus has infected and killed millions of individuals worldwide without discrimination. Due to the lack of SARS-CoV-2-specific treatment options and rapidly mutating variants, the virus triggered waves of infection and death. Computer-assisted drug design techniques have allowed rapid virtual screening and molecular docking for the identification of numerous biological hit compounds. This study used the Schrodinger software to perform high-throughput virtual screening on a flavonoid derivative database consisting of 2055 compounds against the SARS-CoV-2 main protease 6LU7. The Glide Docking scores narrowed the database to ten hit molecules with the PubChem CIDs 1882879, 1866522, 941256, 5703289, 626515, 1974731, 654250, 5490127, 941927, and 5282073. Their scores ranged between -8.073, -7.981, -7.754, -7.933, -7.911, -7.903, -7.875, -7.854, - 7.826, and -7.821 kcal/mol, respectively. They were also studied for their binding properties, including binding interactions, binding orientation and binding energies. The compounds had hydrogen bonds ranging from 1 to 3, and the hydrogen bond interacting residues were HID 164, LEU 141, GLU 166, SER 144, HID 163, and GLY 143. Significantly inhibiting the main protease activity of SARS-CoV-2 are ligands that are capable of creating hydrogen bond interactions with these amino acids, which are considered invaluable during viral replication and transcription. Ergo, these findings suggest that such compounds might indeed inhibit the SARS-CoV-2 main protease 6LU7. These compounds can be developed into viable drug candidates following structural optimization, in vitro studies, in vivo studies, and human clinical trials. Hopefully, other scientists can use the results of this study to develop lifesaving treatments for those affected by the SARS-CoV-2 virus.