Pharmacophore Modelling, Virtual Screening, and Molecular Docking Simulations of Natural Product Compounds as Potential Inhibitors of Ebola Virus Nucleoprotein Ebola virus (EBOV) prevails as a serious public health issue which infected at least 27,000 people and claimed the lives of about 11,000 people in the latest Ebola outbreak in 2014. Although the virus has been known for almost 40 years, currently there is no approved drug for this virus. Hence, the development of a new drug candidate for Ebola is required to anticipate the future outbreak that may happen. In this research, about 229,538 natural product (NP) compounds were retrieved and screened using a computational approach against EBOV nucleoprotein (NP). In the beginning, all NP compounds were screened throughout computational toxicity and druglikeness prediction tests, followed by pharmacophorebased virtual screening and molecular docking simulation to identify their binding affinity and molecular interaction in the RNAbinding groove of EBOV NP. All of the results were compared to 18xcexb2glycyrrhetinic acid, the standard molecule of EBOV NP. In the end, about five NP compounds (UNPD213871, UNPD199951, UNPD124962, UNPD139843, and UNPD147202) were identified to have exciting activities against EBOV NP. Therefore, based on the results of this study, these compounds appeared to have potential inhibition activities against EBOV NP and can be proposed for further in silico and in vitro studies.

Identification Novel Peptides Conjugated to HIV1 Tat Peptide to Inhibit Ebola Virus Entry by Targeting Niemann Pick C1 Protein Ebola virus (EBOV) is the causative agent of Ebola hemorrhagic fever. Currently, there is no effective drug to treat EBOV infection. Niemann Pick C1 (NPC1) is one of the proteins involved in cholesterol homeostasis which emerge as an essential protein in EBOV entry process into the cell. In this research, a series of pharmacophorebased virtual screening and molecular docking simulations were performed to investigate the most potent peptide conjugated to HIV1 Tat peptide as a drug candidate inhibiting NPC1 protein. About 47,512 peptide compounds from NCBI PubChem database, which selected as ligands inhibitor, were screened to eliminate undesired properties. Then, about 12,863 peptides underwent virtual screening, rigid docking, and flexible docking simulations to obtain ligands with favorable inhibition activities. Nine selected ligands with lower Gibbs free binding energy value compared to standard ligand were conjugated to HIV1 Tat peptide to accumulate them inside the endosome, and the inhibition activity was recalculated by flexible docking simulation. Only three ligands, Alarelin, Neurokinin beta, and Callitachykinin I displayed better affinity and minimal conformation changes in the interaction compared to its unconjugated ligand. Then, the potential ligands underwent ADMETox prediction by using AdmetSAR, Toxtree, DataWarrior, and pkSCM software. Three ligands ccallitachykinin, cneurokinin beta, and calarelin showed favorable characteristics as a new drug candidate for the NPC1 inhibitor according to the interaction of the amino acid residues, RMSD, and Gibbs free binding energy.