Our results show that recombinant mAb LZY3412 has high-affinity with the E proteins of three viruses, with the kinetically derived binding affinity (KD) values of 440 and 482.5 nM against JEV-E protein and ZIKV-E protein, respectively; recombinant mAb LZY3412 can efficiently neutralize JEV and ZIKV infections in vitro, with the NT50 values of 19.9 ng/mL and 631 ng/mL, respectively; application of recombinant mAb LZY3412 can significantly improve the percentage survival and reduce the serum viral loads of neonatal mice infected with JEV or ZIKV. The gene discussed is PROS1; the disease is infection.