Effect of Early pregnancy associated protein-1 on Spike protein and ACE2 interactions: Implications in SARS Cov-2 vertical transmission

• Published in: Placenta (Eastbourne) Vol. 152; pp. 39 - 52
• Main Authors: Voina, Vidya Chitta, Swain, Sarita, Kammili, Nagamani, Mahalakshmi, G., Muttineni, Radhakrishna, Chander Bingi, Thrilok, Kondapi, Anand K.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.07.2024
• Subjects: ACE2; Anti-viral; Early pregnancy; Early pregnancy-associated Protein-1; Receptor binding domain protein; SARS Cov-2; Spike protein; ACE2; Anti-viral; Spike protein; Early pregnancy; SARS Cov-2; Receptor binding domain protein; Early pregnancy-associated Protein-1
• ISSN: 0143-4004; 1532-3102; 1532-3102
• DOI: 10.1016/j.placenta.2024.05.128

Several factors influence transmission of 2019-nCoV from mother to fetus during pregnancy, thus the dynamics of vertical transmission is unclear. The role of cellular protective factors, namely a 90 KDa glycoprotein, Early pregnancy-associated protein (Epap-1), expressed by placental endothelial cells in women during early pregnancy would provide an insight into role of placental factors in virus transmission. Since viral spike protein binding to the ACE2 receptors of the host cells promotes virus invasion in placental tissue, an analysis of effects of Epap-1 on the Spike-ACE2 protein binding was studied. Epap-1 was isolated from MTP placental tissue. Molecular interaction of Epap-1 and variants of the spike was analyzed in silco. The interaction of Epap-1 with Spike and RBD were analyzed using ELISA and immunofluorescence studies. The results in silico showed an interaction of Epap-1 with S-protein at RBD region involving K417, Y449, Y453, Y456, Y473, Q474, F486, Q498, N501 residues of spike with Y61, F287, I302, N303, N305, S334, N465, G467, N468 residues of Epap-1 leading to interference of S-protein and ACE2 interaction [1]. Further, the interaction is conserved among the variants. The studies in vitro confirm that Epap-1 affects S protein-ACE2 and RBD- ACE2 binding, thus suggesting that during early pregnancy, SARS CoV-2 infection may be protected by Epap-1 protein present in placental tissue. The results were further confirmed by pseudovirus expressing Spike and RBD in an infection assay. Epap-1 interferes with Spike and RBD interaction with ACE2, suggesting a possible mechanism of the antiviral environment during pregnancy. •Glycoprotein present in early pregnancy, Epap-1, show interaction with RBD region of Spike protein of SARS Cov-2.•Epap-1 interactions showed stronger in omicron, delta than Wuhan variant.•Epap-1 showed an inhibition of Spike and RBD protein binding to ACE2.•Epap-1 showed neutralization of psuedovirus expressing Spike and RBD.