Glycoprotein attachment with host cell surface receptor ephrin B2 and B3 in mediating entry of nipah and hendra virus: a computational investigation.

ABSTRACT

Nipah virus (NiV) and Hendra virus (HeV) are highly pathogenic paramyxovirus which belongs to Henipavirus family, causes severe respiratory disease, and may lead to fatal encephalitis infections in humans. NiV and HeV glycoproteins (G) bind to the highly conserved human ephrin-B2 and B3 (EFNB2 & EFNB3) cell surface proteins to mediate the viral entry. In this study, various molecular modelling approaches were employed to understand protein-protein interaction (PPI) of NiV and HeV glycoprotein (84% sequence similarity) with Human EFN (B2 and B3) to investigate the molecular mechanism of interaction at atomic level. Our computational study emphasized the PPI profile of both the viral glycoproteins with EFN (B2 and B3) in terms of non-bonded contacts, H-bonds, salt bridges, and identification of interface hotspot residues which play a critical role in the formation of complexes that mediate viral fusion and entry into the host cell. According to the reports, EFNB2 is considered to be more actively involved in the attachment with the NiV and HeV glycoprotein; interestingly the current computational study has displayed more conformational stability in HeV/NiV glycoprotein with EFNB2 complex with relatively high binding energy as compared to EFNB3. During the MD simulation, the number of H-bond formations was observed to be less in the case of EFNB3 complexes, which may be the possible reason for less conformational stability in the EFNB3 complexes. The current detailed interaction study on the PPI may put a path forward in designing peptide inhibitors to obstruct the interaction of viral glycoproteins with host proteins, thereby inhibiting viral entry. Graphical abstract The viral attachment and fusion of Nipah and Hendra virus was explored through the interaction between viral glycoprotein and the host cell surface ephrin protein. The MD simulation results displayed more stability in Nipah and Hendra glycoprotein with EFNB2 as compared to EFNB3. The residue Glu533 in the central cavity of HeV/NiV glycoprotein protein identified as the potential hotspot in binding with the G-H loop of EFNB2. Supplementary Information The online version contains supplementary material available at 10.1007/s12039-022-02110-9.