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1. Identifying the Zoonotic Origin of SARS-CoV-2 by Modeling the Binding Affinity between the Spike Receptor-Binding Domain and Host ACE2

   https://doi.org/10.1021/acs.jproteome.0c00717  

   Huang, Xiaoqiang; Zhang, Chengxin; Pearce, Robin; Omenn, Gilbert S.; Zhang, Yang (December 2020, Journal of Proteome Research)

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2. Atomistic insights into the binding of SARS-CoV-2 spike receptor binding domain with the human ACE2 receptor: The importance of residue 493

   https://doi.org/10.1016/j.jmgm.2022.108360  

   Carter, Camryn; Airas, Justin; Parish, Carol A. (January 2023, Journal of Molecular Graphics and Modelling)
3. Binding behavior of receptor binding domain of the SARS-CoV-2 virus and ivermectin

   https://doi.org/10.1038/s41598-024-53086-0  

   Gossen, Kasidy R; Zhang, Meiyi; Nikolov, Zivko L; Fernando, Sandun D; King, Maria D (December 2024, Scientific Reports)

   Abstract The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), sparked an international debate on effective ways to prevent and treat the virus. Specifically, there were many varying opinions on the use of ivermectin (IVM) throughout the world, with minimal research to support either side. IVM is an FDA-approved antiparasitic drug that was discovered in the 1970s and was found to show antiviral activity. The objective of this study is to examine the binding behavior and rates of association and dissociation between SARS-CoV-2 receptor binding domain (RBD), IVM, and their combination using aminopropylsilane (APS) biosensors as surrogates for the hydrophobic interaction between the viral protein and human angiotensin-converting enzyme 2 (ACE2) receptors to determine the potential of IVM as a repurposed drug for SARS-CoV-2 prevention and treatment. The IVM, RBD, and combination binding kinetics were analyzed using biolayer interferometry (BLI) and validated with multiple in silico techniques including protein–ligand docking, molecular dynamics simulation, molecular mechanics-generalized Born surface area (MM-GBSA), and principal component analysis (PCA). Our results suggest that with increasing IVM concentrations the association rate with the hydrophobic biosensor increases with a simultaneous decrease in dissociation. Significant kinetic changes to RBD, when combined with IVM, were found only at a concentration a thousand times the approved dosage with minimal changes found over a 35-min time period. Our study suggests that IVM is not an effective preventative or treatment method at the currently approved dosage. 

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4. Intra- and intermolecular atomic-scale interactions in the receptor binding domain of SARS-CoV-2 spike protein: implication for ACE2 receptor binding

   https://doi.org/10.1039/d0cp03145c  

   Adhikari, Puja; Li, Neng; Shin, Matthew; Steinmetz, Nicole F.; Twarock, Reidun; Podgornik, Rudolf; Ching, Wai-Yim (September 2020, Physical Chemistry Chemical Physics)

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   The COVID-19 pandemic poses a severe threat to human health with unprecedented social and economic disruption. Spike (S) glycoprotein in the SARS-CoV-2 virus is pivotal in understanding the virus anatomy, since it initiates the early contact with the ACE2 receptor in the human cell. The subunit S1 in chain A of S-protein has four structural domains: the receptor binding domain (RBD), the n-terminal domain (NTD) and two subdomains (SD1, SD2). We report details of the intra- and inter-molecular binding mechanism of RBD using density functional theory, including electronic structure, interatomic bonding and partial charge distribution. We identify five strong hydrogen bonds and analyze their roles in binding. This provides a pathway to a quantum-chemical understanding of the interaction between the S-protein and the ACE2 receptor with insights into the function of conserved features in the ACE2 receptor binding domain that could inform vaccine and drug development. 

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5. DFT study of ligand binding in the β1 adrenergic receptor

   https://doi.org/10.1016/j.comptc.2021.113208  

   Safarian, Daryna; Simons, Megan; Evans, Rebecca G.; Peterson, Larryn W.; Cafiero, Mauricio (May 2021, Computational and Theoretical Chemistry)

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