Background: Lassa Virus (LV) infection is an 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 a key to develop drug candidates for the treatment of LV infection.
Methods: Molecular dynamic 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 a complete loss of saltbridge
interaction between lysine e-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
seems to have a seemingly redundant interaction with C5-O2P. While S247A is only associated
with the 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 a loss of ssRNA interaction
may negatively affect genome biochemistry, semi-viable Lassa viron in S247A mutation
may be due to the loss of 3D arrangement of ssRNA due to splayed out nucleotides.