IN SILICO STUDY OF BIOACTIVE PEPTIDES AS SARS COV-2 PROTEASE INHIBITORS

• Main Author: Iqbal Rhamadianto, Muhamad
• Format: Theses
• Language: Indonesia
• Online Access: https://digilib.itb.ac.id/gdl/view/85519
• Institution: Institut Teknologi Bandung

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS CoV-2) emerged in 2019 in Wuhan, China, and has since caused a global pandemic known as COVID-19. In 2024, the World Health Organization tracked several new variants of SARS CoV2 that could potentially evade immune responses and increase transmissibility. Proteases are promising targets for the treatment of COVID-19, but the development of antiviral compounds that are effective against proteases is still a very complicated process. Bioactive peptides are known to have antiviral activity and are known as antiviral peptides. The aim of this study is to find bioactive peptides that can be used as an alternative treatment for SARS CoV-2 by inhibiting proteases in silico. Pharmacophore modelling of 6 training set compounds was made to screen 168,420 peptides to obtain 1000 peptide molecules which were then subjected to Molecular docking-based virtual screening. Molecular dynamics simulations were performed on the Co-crystalized ligand, mol-nupiravir, lopinavir, and the 2 best test ligands from previous studies. In TMPRSS2, the test ligands T1 (L-asparticyl-L-alanyl-L-prolyl-L-alanine) and T3 (L-glutaminylL-tryptophyl-Ltryptophyl-L-isoleucine) had lower binding free energy values of ?13.4161 kcal/mol and ?12.5469 kcal/mol compared to the Co-crystalized ligands, lopinavir and molnupiravir. In the main protease, the test ligands M1 (L-phenylalanyl-Ltryptophyl-L-prolylL-isoleucine) and M3 (L-glutaminyl-L-tryptophyl-L-tryptophyl- L-isoleucine) had binding binding afinityof ?63.6759 kcal/mol and ?35.0534 kcal/mol, lower than those of the Co-crystalized ligands, lopinavir and molnupiravir. In furin the binding afinity of the co-crystalized ligands were lower than those of the test ligands, molnupiravir and lopinavir. In Papain like Protease the test ligand P3 (L-tryptophyl-L-phenylalanyl-L-threonine) have interaction with the important amino acid. Thus, T1, T3, M1, M3 and P3 have potential as inhibitors of Main Protease, TMPRSS2 and Papain like Protease in SARS CoV-2 .