_applied sciences_  
_Article_  
**Lumateperone Interact with S-Protein of _Ebola_ Virus and TIM-1 of Human Cell Membrane: Insights from**  
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Footnote  
The \(GP\) gene encodes the surface glycoprotein (GP). It has vital roles in the pathogenesis and infection of the virus, and during virus replication, its expression is tightly controlled [3]. It has been documented recently that the level of GP1 and GP2 expression controls the production and release of the virus [4]. The _Ebola_ virus comprises different structural proteins such as spike (S), envelope (E), membrane (M), and the nucleocapsid (N) proteins [4]. The S-protein is glycoprotein in nature. In human cells, the _Ebola_ virus enters through the binding of the surface spike protein with a receptor protein (T-cell immunoglobulin mucin mucin domain-1 (TIM-1)) present on the membrane of human cells. This facilitates the virus-host cell membrane fusion and receptor binding. A schematic representation of the inhibition of the virus S-protein through Lumateperone is shown in Figure 1.  
In the endosomal compartment of human cells, several cell surface receptors facilitate filovirus attachment and incorporation, i.e., phosphatidylinositolserine (PS) receptors [5; 6] and C-type lectin receptors [7; 8]. PS receptors do not bind with the virus glycoprotein (GP) but interact with PS on the surface of the virion lipid membrane, which causes the incorporation of virus particles into the endosomal compartment [6; 9]. This process of viral entry is known as apoptotic mimicry [10; 11].  
The T-cell immunoglobulin mucin domain (TIM) family is one of the most important families of PS receptors [12]. The type I cell surface glycoproteins (GPs) are members of the TIM protein family. Whereas in mice the functional family members are four, TIM-1, TIM-2, TIM-3, and TIM-4\({}^{\prime\prime}\), in humans there are only three: \"TIM-1, TIM-3, and TIM-4\({}^{\prime\prime}\). Murine TIM-1 (mTIM-1) and mTIM-4 and human TIM-1 (hTIM-1) and hTIM-4 can assist as enveloped viral receptors, while the other members cannot [11; 12].  
Previously, Lumateperone has been reported as a serotonin transport inhibitor. It causes inhibition in a mesolimbic-specific manner, raising the glutamatergic N-methyl-D-aspartate (NMDA) GluN2B receptors phosphorylation in the human body [13]. There is no  
Figure 1: Graphical representation of the binding of the viral S-protein with the TIM-1 cellular receptor. The presence of Lumateperone inhibits the S-protein and TIM-1 interaction and eventually prevents viral entry into the cell.  
information about the binding of Lumateperone with the S-protein of the _Ebola_ virus and its host cells cognate receptor TIM-1.  
Through this backdrop, the current study examines the binding of Lumateperone with the virus S-protein and the host cells cognate receptor TIM-1 using computational methods. The computational methods (molecular docking and simulation) are the best approaches to study this type of binding mechanism before experimental studies, which are costly and take more time.  
In addition, the enhancement in the reliability, speed, and accuracy of computational docking approaches in last few years make it an appropriate alternative to drug design, which is structure-based. The current study includes molecular modeling and docking results of Lumateperone with the S-protein of the _Ebola_ virus along with the host cell TIM-1, which is a virus S-protein cognate receptor in the human body.