Screening of Potential Northern African Natural Product Compounds as Dengue Virus NS5 Methyltransferase Inhibitor: An in Silico Approach Dengue virus (DENV) has emerged as one of the most prevalent viruses in subtropical countries, yet there is no commercial drug available to combat DENV infection effectively. The RNAcapping and replication processes of DENV are regulated by NS5 methyltransferase (MTase). Hence, NS5 MTase is believed as a promising drug target for DENV. In this research, the DENV NS5 MTase was subjected to 6,842 Northern African Natural Product Database (NANPDB) compounds through computational simulation methods. Three crystal structures of DENV NS5 MTase, which contained Sadenosylhomocysteine (PDB ID: 4V0Q), Sadenosylmethionine (PDB ID: 3P97), and sinefungin (PDB ID: 4R8S), were used as the core template of the pharmacophore mapping in the SAHbinding site of DENV NS5 MTase. Four amino acid residues (Glu111, Asp131, Val132, and Asp146) were found to strongly interacted with SAH, SAM, and SFG, indicating that these residues may hold a vital role on the catalytic activity of DENV NS5 MTase. From the docking simulations, three ligands showed favorable inhibition activities by having lower xcex94Gbinding value than the standard ligands. Rutin has the lowest xcex94Gbinding value at 12.3586 kcalmol, followed by isorhamnetin 3rutinoside (12.3203 kcalmol), and tetraogalloyl glucose (12.2039 kcalmol). Pharmacological properties of these ligands were analyzed; no potential harmful effect was detected. Therefore, these ligands can be suggested as drug candidates for treating DENV infection by targeting SAHbinding site of NS5 MTase. The ligands efficacy needs to be validated through a series of in vitro, in vivo and clinical studies.

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.