RT Journal Article
SR Electronic
T1 Identification of human immunodeficiency virus -1 E protein-targeting lead compounds by pharmacophore based screening
JF Saudi Medical Journal
JO Saudi Med J
FD Prince Sultan Military Medical City
SP 1324
OP 1332
DO 10.15537/smj.2022.43.12.20220599
VO 43
IS 12
A1 Almehmadi, Mazen M.
A1 Shafie, Alaa A.
A1 Allahyani, Mamdouh
A1 Muhammad, Tahir
A1 Baammi, Soukayna
A1 Aljuaid, Abdulelah
A1 Almalki, Abdulraheem A.
A1 Alsaiari, Ahad Amer
A1 Ashour, Amal Adnan
YR 2022
UL http://smj.org.sa/content/43/12/1324.abstract
AB Objectives: To identify potential compounds by seeking the knowledge of molecular interactions between human immunodeficiency virus (HIV) glycoprotein (gp) 120 protein and anti-HIV drug (BMS-488043).Methods: This study is a computational structure-based drug design study, carried out at University of Taif, Saudi Arabia and African Genome Centre (AGC), Mohammed VI Polytechnic University, Benguerir, Morocco from January 2021 to March 2022. Initially, using the docked structure of gp120 with BMS-488043, a structure-based pharmacophore model was created. The generated model was utilized for virtual screening of the ZINC and ChemBridge database in order to identify hit compounds. To further assess the time-dependent stability of the selected complexes, computer simulation was performed.Results: From pharmacophore-based screening, 356 hits were obtained from both the database. The docking studies of the retrieved hit compounds reveal that all the compounds fit into the binding site of gp120. However, based on the significant interactions with the crucial residues and docking scores four compounds were suggested as potential hits. MD simulation of ChemBridge14695864 and ZINC06893293 in complex with gp120 suggested that both compounds significantly stabilized the receptor.Conclusion: These findings could aid in the design of effective drugs against HIV by inhibiting the interaction between gp120 and CD4.