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-MartÃnez 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.