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

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 fo...

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Published inApplied 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
LanguageEnglish
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
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Summary: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.
ISSN:2076-3417
2076-3417
DOI:10.3390/app12178820