In silico and in vitro evaluation of imatinib as an inhibitor for SARS-CoV-2. Issue 7 (3rd May 2023)

• Record Type: Journal Article
• Authors: Mulgaonkar, Nirmitee; Wang, Haoqi; Mallawarachchi, Samavath; Růžek, Daniel; Martina, Byron; Fernando, Sandun
• Is Part Of: Journal of biomolecular structure & dynamics. Volume 41:Issue 7(2023)
• Page Start: 3052
• Page End: 3061
• Publication Date: 2023-05-03
• Subjects: SARS-CoV-2 -- COVID-19 -- betacoronavirus -- acute respiratory disease -- Wuhan -- ACE2 -- surface structural spike glycoprotein -- molecular docking -- Bcr-Abl tyrosine kinase inhibitor -- imatinib; Biomolecules -- Periodicals; Molecular structure -- Periodicals; Molecular Biology -- Periodicals; Biomechanics -- Periodicals; 572
• DOI: 10.1080/07391102.2022.2045221
• Languages: English
• ISSNs: 0739-1102

Abstract

Abstract: The rapid geographic expansion of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the infectious agent of Coronavirus Disease 2019 (COVID-19) pandemic, poses an immediate need for potent drugs. Enveloped viruses infect the host cell by cellular membrane fusion, a crucial mechanism required for virus replication. The SARS-CoV-2 spike glycoprotein, due to its primary interaction with the human angiotensin-converting enzyme 2 (ACE2) cell-surface receptor, is considered a potential target for drug development. In this study, around 5, 800 molecules were virtually screened using molecular docking. Five molecules were selected for in vitro experiments from those that reported docking scores lower than −6 kcal/mol. Imatinib, a Bcr-Abl tyrosine kinase inhibitor, showed maximum antiviral activity in Vero cells. We further investigated the interaction of imatinib, a compound under clinical trials for the treatment of COVID-19, with SARS-CoV-2 RBD, using in silico methods. Molecular dynamics simulations verified that imatinib interacts with RBD residues that are critical for ACE2 binding. This study also provides significant molecular insights on potential repurposable small-molecule drugs and chemical scaffolds for the development of novel drugs targeting the SARS-CoV-2 spike RBD. Communicated by Ramaswamy H. Sarma