Preparation and mutation

The X-ray-derived 3D crystal structures of ephrin-B2 (PDB ID: 2VSM), and ephrin-B3 (PDB ID: 3D12) were attained from the RCSB Protein Data Bank website [28, 29]. Since 2VSM contains Nipah henipavirus Hemagglutinin-neuraminidase in complex with human cell surface receptor ephrin-B2, first, the G protein was removed from the PDB file using UCSF Chimera 1.16 software [30]. Therefore, only chain ephrin-B2 with 140 sequence length along with one NAG group (2-acetamido-2-deoxy-beta-D-glucopyranose) remained. This NAG group was not considered in the following analysis because our goal was to repurpose drugs and not co-crystal molecules. The 3D12 PDB file contains Ephrin-B3 with 141 sequence lengths and two non-standard residues (HOH and SO4). On the other hand, the reference NiV-Malaysia and NiV-Bangladesh strains were generated based on GenBank accession numbers {"type":"entrez-nucleotide","attrs":{"text":"AJ627196.1","term_id":"57282808","term_text":"AJ627196.1"}}AJ627196.1 and {"type":"entrez-nucleotide","attrs":{"text":"AY988601.1","term_id":"66271892","term_text":"AY988601.1"}}AY988601.1 respectively [31] using SWISS-MODEL [32]. The critical glycoprotein substitutions in two main variants Malaysia (GM) and Bangladesh (GB) could be observed in Supplementary Fig. 1. Based on Shamsi et al. [33] review study, seven potential drugs with clinical effectiveness in COVID-19 therapy which target human ACE2 receptor and SARS-CoV-2 Spike protein were used as specific inhibitors against human ephrin-B2, ephrin-B3 receptors and Nipah virus Glycoprotein in two Malaysia and Bangladesh strains [33]. In fact, Pemirolast, Nitrofurantoin, Isoniazid Pyruvate, and Eriodictyol which are specific ACE2 inhibitors were repurposed for human ephrin-B2 and ephrin-B3 receptors, and Cepharanthine, Ergoloid, and Hypericin drugs which are targeting SARS-CoV-2 Spike protein were analyzed against Nipah virus Glycoprotein. The SDF format of each drug was obtained from the ZINC15 free database [34].