3.3 Identifying potential Marburg virus VP35 from anti-viral phytochemical compounds of Spondias mombin leaf extracts
Having identified several potential anti-viral compounds from the leaf extracts Spondias mombin , we employed molecular modelling techniques, particularly molecular docking, to identify potential MARV VP35 inhibitors from the identified antiviral phytochemical compounds. Molecular docking has been widely used in recent years to identify potential binders to various biological molecules and has also aided in speeding up the design and discovery of novel therapeutic agents at a relatively lower cost (Dar and Mir, 2017, Zoete et al., 2009, Prieto-Martínez et al., 2019).
Therefore, to identify which of the phytochemical compounds in this report would exhibit potency in treating Marburg virus (MARV), molecular docking of each compound into the inhibitor binding domain of MARV VP35 was performed using AutoDock Vina (Trott and Olson, 2010). MARV VP35 is a unique multi-functional protein encoded by all filoviruses. As shown in Figure 1 , MARV VP35 exhibits a sequence similarity of 42% with Ebola virus (EBOV) VP5 with over 70% sequence similarity in their inhibitor binding domains. VP35 as a crucial protein is implicated in viral pathogenesis, including viral mRNA synthesis and replication of the negative-sense RNA viral genome, whose therapeutic modulation could lead to the discovery of novel anti-filoviral therapeutic agents (Peterson et al., 2006, Martini et al., 1968, Bausch et al., 2003).
In performing the molecular docking, the inhibitor binding domain of MARV VP35 was identified by superimposing the inhibitor bound EBOV VP35 complex (PDB code: 4BIC) with MARV VP35 (PDB code: 4GHA), as shown inFigure 1 . Using the grid box component of AutoDock Vina, a grid box with centre dimensions; x=13.45, y=33.63, z=31.69 and size dimensions; x=12.67, y=15.97, z=15.19.