Background: Lassa virus (LV) infection is a endemic disease from West Africa posing threat to the entire world. A thorough understanding of the mechanistic workings of the genome products of LV may be key to developing drugs candidates for the treatment of LV infection.
Methods: Molecular dynamics simulation has been used to provide insight into the mechanistic basis for total loss of ssRNA interaction in nucleoprotein (NP) K309A, partial loss in S247A, and no loss in S237A by following the hydrogen bond interaction, water influx into the ssRNA pocket and glycosidic torsion angle (χ) of the ssRNA.
Results: The results revealed that K309A mutation is associated with complete loss of salt-bridge interaction between lysine ε-amino and U4-O2P phosphodiester linkage but not in S237A where S247-OG atom played a redundant role. S247A is also associated with partial loss of hydrogen bond between OG atom of S247 and C5-O2P phosphodiester bond as T178-OG1 group seem to have a seemingly redundant interaction with C5-O2P. While S247A only is also associated with alteration of χ rotation in U6/C7, both K309A and S247 but not S237A is associated with increased water influx into the ssRNA binding pocket.
Conclusion: K309A mutation may result in non-viable Lassa viron as loss of ssRNA interaction may negatively affect genome biochemistry, semi-viable Lassa viron in S247A mutation may be due to loss of 3D arrangement of ssRNA due to splayed out nucleotides.