Lumateperone Interact with S-Protein of Ebola Virus and TIM-1 of Human Cell Membrane: Insights from Computational Studies

• Published in: Applied sciences Vol. 12; no. 17; p. 8820
• Main Authors: Muzammal, Muhammad, Firoz, Ahmad, Ali, Hani Mohammed, Farid, Arshad, Khan, Muzammil Ahmad, Hakeem, Khalid Rehman
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 01.09.2022
• Subjects: Attraction; Binding energy; Cell membranes; Computer applications; Design; Ebola virus; Ebolavirus; Energy; Glycoproteins; Immunoglobulins; Ligands; Lumateperone; Molecular modelling; Proteins; S-protein/TIM-1 complex; Simulation; Simulation analysis; Spike protein; Strategy; Thermodynamics; Viral diseases; Viruses
• DOI: 10.3390/app12178820
• ISSN: 2076-3417

The Ebola virus outbreak in Africa is an unparalleled risk to society and to human health. Interventions that utilize the host cell receptor TIM-1 and the viral spike protein (S-protein) can be considered effective and suitable treatments. Initially, we identified Lumateperone as a candidate drug for the S-protein using the LEA3D tool; then using molecular modeling and docking, we investigated the binding efficiency of Lumateperone with the S-protein and its TIM-1 receptor. The present computational study shows that Lumateperone possesses a strong attraction to the S-protein and the TIM-1 receptor of the host as well as to their complex. It was observed that the binding energy of the S-protein/TIM-1 complex decreases in the presence of Lumateperone. A significant decrease of 395.75 kJ/mol (Lumateperone bound to the S-protein) and 517.19 kJ/mol (Lumateperone bound to the TIM-1 receptor) of binding energy was observed in the S-protein/TIM-1 complex in the presence of Lumateperone compared to their direct binding. We also noticed that Lumateperone was binding with the residues in the S-protein (Asn461) and the TIM-1 (Trp274 and Asn275) receptor that were involved in making the S-protein/TIM-1 complex. In the presence of Lumateperone, the simulation analysis also supports the above findings on the effectiveness of Lumateperone in delaying the establishment of the complex of the S-protein/TIM-1. In conclusion, this computational study predicts the possibility of Lumateperone as a therapeutic strategy against the Ebola virus.