Computational Electrostatics Predict Variations in SARS-CoV-2 Spike and Human ACE2 Interactions

Abstract

SARS-CoV-2 is a novel virus that crossed over into humans in 2019 and declared a pandemic in early 2020. To understand how the virus infects a new host, we need to understand the mechanistic functions involved with the binding process. To address this need, we generate homology models of SARS-CoV-2 spikes as monomer and trimer to determine the feasibility of reduced computational requirements by using monomer structures. We further generate homology models of the conserved region of SARS-CoV-2 spike subunit s1 noted as the receptor binding domain (RBD) and the human angiotensin-converting enzyme 2 (ACE2). To determine functional breadth of spike monomer, trimer and RBD in relation with ACE2, we apply Coulombs Law to determine an electric force between combinations with ACE2 across the range of pH from 3.0 to 9.0 in 0.1 increments. The results indicate that spike trimer should be used to determine mechanistic binding function and these data indicate that variations of spike sequence influence breadth of function. Our results also indicate the RBD has a broader range of function across pH compared to spike trimer, but is influenced by the range of function presented by the spike trimer.