Results and Discussion 2.1. that this 10H10 antibody recognizes the amino acid sequence between the two cysteines C92-C116 of the fusion loop (FL) region of flaviviruses E proteins. Overall, our results indicate that this antibody-antigen complex can form a rigid or dynamic structure that provides antibody cross reactivity and efficient interaction with the fusion loop of E protein. Keywords: flavivirus, TBEV, WNV, ZIKV, DENV, monoclonal antibody, Retinyl acetate recombinant protein, ELISA, molecular protein docking, molecular protein dynamic 1. Introduction In recent years, there has been a constant increase in infectious diseases caused by viruses from the family [1,2]. The family is usually represented by four genera comprising of 89 known virus species. All viruses of the family share the genome structure and the amino acid homology of major structural proteins [3,4]. Diseases induced by the viruses of the family such as dengue virus (DENV), West Nile virus (WNV), tick-borne encephalitis virus (TBEV), Japanese encephalitis virus (JEV) and Zika virus (ZIKV) are among the most life-threatening emerging infections that lead to more than 500,000 annual hospitalizations with a mortality rate of about 5%, caused by hemorrhagic fever, shock syndrome, and tissue and capillaries damage [5,6,7,8,9]. There are effective inactivated vaccines against JEV, TBEV, and an attenuated vaccine against yellow fever virus (YFV) [10,11,12]. However, the development of vaccines against DENV, WNV and ZIKV is usually complicated probably due to the antibody-dependent enhancement (ADE) of infections [13,14,15]. An alternative to the vaccine may be serum therapy. However, obtaining specific immunoglobulins from donors blood is limited by material availability and possible viral contamination. In addition, possible antibody-dependent disease severity enhancement also significantly Retinyl acetate limits the use of serum therapy [13,14,15]. In some cases, monoclonal antibodies (mAb) can be used for flavivirus-infection therapy. Currently, several monoclonal neutralizing antibodies (NAb) against flaviviruses are available [4]. The targets recognized by neutralizing antibodies are usually the membrane protein precursor [16], nonstructural protein 1 (NS1) [17], and envelope protein (E protein) [18]. The Retinyl acetate E protein is usually involved in the binding of virus particles to cell receptors that mediate the penetration of the viruses to host Retinyl acetate cells. This feature makes the E protein an attractive target for NAb development. The extracellular part of the E protein consists of the following three domains: the central ?-barrel domain name I (DI), which is connected to the dimerization domain name II (DII), and the binding domain name to the Ig-like receptor III (DIII) [4]. DII contains a hydrophobic sequence, called the fusion loop (FL), which is usually conserved among CACN2 most species [4]. FL is usually immersed in the host cell membrane during pH-induced conformational changes. This process results in the fusion of viral and Retinyl acetate host cell membranes [4]. Neutralizing antibodies against the E protein can inhibit several processes during contamination, including binding to cellular receptors, blocking conformational changes, and affecting FL function, thereby preventing viral particle entry to the host cells [4]. The FL region of the E protein is usually highly conserved for all those flaviviruses and may be a potential target blocking virus entry to the host cells. Several antibodies against this region have been developed and described, including 3G9 [19], POWV-56 [20], 2A10G6 [21], E53 [22] and 758P6B10 [23]. However, the above antibodies interacting with the FL region have limited neutralization efficacy due to FL conformation in accessing mature virions. The FL region becomes accessible for antibodies only during the fusion between the viral and host cell membrane [4]. The ADI-15878 and VRC34.01 antibodies recognize the FL region of E proteins in Ebola and HIV-1 viruses and are capable of blocking virus entry to the host cells with high efficiency [24,25,26]. Previously, we decided and described mouse monoclonal non-neutralizing Ab 10H10 that interacts with TBEV and many other flaviviruses [27]. The data suggest.