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.

背景：拉沙病毒（LV）感染是一种来自西非的地方病，对全世界构成威胁。彻底了解 LV 基因组产物的机制可能是开发用于治疗 LV 感染的候选药物的关键。

方法：分子动力学模拟已被用于通过跟踪氢键相互作用、水流入 ssRNA 来深入了解核蛋白 (NP) K309A 中 ssRNA 相互作用完全丧失、S247A 部分丧失和 S237A 无丧失的机制基础ssRNA的口袋和糖苷扭转角（χ）。

结果：结果显示，K309A 突变与赖氨酸 e-氨基和 U4-O ₂ P 磷酸二酯键之间盐桥相互作用的完全丧失有关，但在 S237A 中没有，其中 S247-OG 原子起到了多余的作用。S247A 也与 S247 的 OG 原子和 C5-O ₂ P 磷酸二酯键之间氢键的部分丢失有关，因为 T178-OG1 基团似乎与 C5-O ₂ P有一个看似多余的相互作用。而 S247A 仅与改变有关U6/C7 中的 χ 旋转，K309A 和 S247 但不是 S237A 与增加的水流入 ssRNA 结合口袋相关。

结论：K309A 突变可能导致无活力的拉沙病毒，因为 ssRNA 相互作用的丧失可能对基因组生化产生负面影响，S247A 突变中的半活力拉沙病毒可能是由于 ssRNA 的 3D 排列丢失，由于核苷酸的展开。