Correlating the differences in the receptor binding domain of SARS-CoV-2 spike variants on their interactions with human ACE2 receptor

Author:

Mahalingam Gokulnath,Arjunan Porkizhi,Periyasami Yogapriya,Dhyani Ajay Kumar,Devaraju Nivedita,Rajendiran Vignesh,Christopher Abisha Crystal,KT Ramya Devi,Dhanasingh Immanuel,Thangavel Saravanabhavan,Murugesan Mohankumar,Moorthy Mahesh,Srivastava Alok,Marepally Srujan

Abstract

AbstractSpike glycoprotein of SARS-CoV-2 variants plays a critical role in infection and transmission through its interaction with human angiotensin converting enzyme 2 (hACE2) receptors. Prior findings using molecular docking and biomolecular studies reported varied findings on the difference in the interactions among the spike variants with the hACE2 receptors. Hence, it is a prerequisite to understand these interactions in a more precise manner. To this end, firstly, we performed ELISA with trimeric spike glycoproteins of SARS-CoV-2 variants including Wuhan Hu-1(Wild), Delta, C.1.2 and Omicron. Further, to study the interactions in a more specific manner by mimicking the natural infection, we developed hACE2 receptors expressing HEK-293T cell line, evaluated their binding efficiencies and competitive binding of spike variants with D614G spike pseudotyped virus. In line with the existing findings, we observed that Omicron had higher binding efficiency compared to Delta in both ELISA and Cellular models. Intriguingly, we found that cellular models could differentiate the subtle differences between the closely related C.1.2 and Delta in their binding to hACE2 receptors. Our study using the cellular model provides a precise method to evaluate the binding interactions between spike sub-lineages to hACE2 receptors.

Funder

Department of Biotechnology, Ministry of Science and Technology, India

Publisher

Springer Science and Business Media LLC

Subject

Multidisciplinary

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