Thermodynamics of the Interaction between the Spike Protein of Severe Acute Respiratory Syndrome Coronavirus-2 and the Receptor of Human Angiotensin-Converting Enzyme 2. Effects of Possible Ligands

Abstract

Since the end of 2019, the coronavirus SARS-CoV-2 has caused more than 1000000 deaths all over the world and still lacks a medical treatment despite the attention of the whole scientific community. Human angiotensin-converting enzyme 2 (ACE2) was recently recognized as the transmembrane protein that serves as the point of entry of SARS-CoV-2 into cells, thus constituting the first biomolecular event leading to COVID-19 disease. Here, by means of a state-of-the-art computational approach, we propose a rational evaluation of the molecular mechanisms behind the formation of the protein complex. Moreover, the free energy of binding between ACE2 and the active receptor binding domain of the SARS-CoV-2 spike protein is evaluated quantitatively, providing for the first time the thermodynamics of virus–receptor recognition. Furthermore, the action of different ACE2 ligands is also examined in particular in their capacity to disrupt SARS-CoV-2 recognition, also providing via a free energy profile the quantification of the ligand-induced decreased affinity. These results improve our knowledge on molecular grounds of the SARS-CoV-2 infection and allow us to suggest rationales that could be useful for the subsequent wise molecular design for the treatment of COVID-19 cases.

Pomegranate peel extract polyphenols attenuate the SARS-CoV-2 S-glycoprotein binding ability to ACE2 Receptor: In silico and in vitro studies

“…In our previous in silico study, we searched for the most druggable binding site on RBD of S-glycoprotein for testing the PoPEx potential for interaction. However, interactions with any of RBD amino-acid residues could potentially interfere with S-glycoprotein and ACE2 receptor contacts [22] . Therefore, in this study, we expanded our docking simulation to the whole S-glycoprotein RBD region and introduced the molecular dynamic simulation to test the ligand-protein dynamics.…”

In silico study of the inhibition of SARS-COV-2 viral cell entry by neem tree extracts

“…1 Several reports have demonstrated that the spike protein is important for the viral life cycle and it is an important target to block viral cell entry. 1,4,15 Currently, computational works have reported peptides and small molecules as inhibitors of the spike RBD. 1,4,[15][16][17][18] However, to the best of our knowledge, there is no study which has reported the antiviral effectiveness of neem extracts as spike RBD-ACE2 inhibitors in silico.…”

Engineering of 2D Materials To Trap And Kill SARS-CoV-2: A New Insight From Multi-Microsecond Atomistic Simulations

“…Researchers have studied the structure [20,21] and the function [22] of spike protein and possible blockers [23][24][25][26] to target and suppress the virus through its spike protein. For instance, Han and Kral [27] designed peptide inhibitors with α-helix structure against spike protein.…”