ABSTRACT
We report protein- and aptamer-based electrochemical biochips for low-cost, one-step, sensitive and accurate multiplex detection of SARS-CoV-2 spike (S) and nucleocapsid (N) proteins, and IgG antibody in unprocessed clinical samples, allowing citizens to achieve rapid diagnosis at home or in community settings.
Subject(s)
Biosensing Techniques , COVID-19 , Antibodies, Viral , COVID-19/diagnosis , Electrochemical Techniques , Humans , Immunoassay , SARS-CoV-2 , Spike Glycoprotein, CoronavirusABSTRACT
The viral entry process of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requires heparin and heparan sulfates from the cell surface, functioning as a cofactor for human angiotensin-converting enzyme 2 (ACE2) for recognizing the receptor-binding domain (RBD) of the spike (S) protein on the surface of the virion. In the present study, the binding poses of an oligosaccharide with four repeating units of GlcNS6S-IdoA2S (octa) predicted by Vina-Carb in the RBD binding site were employed in molecular dynamics (MD) simulations to provide atomic details for studying the cofactor mechanism. The molecular model in the MD simulations reproduced the length- and sequence-dependent behavior observed from the microarray experiments and revealed an important planar U-turn shape for HP/HS binding to RBD. The model for octa with this shape in the ACE2-RBD complex enhanced the interactions in the binding interface. The comparisons with the ACE2-RBD complex suggested that the presence of octa in the RBD binding site blocked the movements in a loop region at the distal end of the RBD binding interface and promoted the contacts of this loop region with the ACE2 N-terminus helix. This study shed light on the atomic and dynamic details for HP/HS interacting with RBD and provided insights into their cofactor role in the ACE2-RBD interactions.
Subject(s)
COVID-19 , Heparin , Angiotensins , Binding Sites , Heparitin Sulfate , Humans , Molecular Dynamics Simulation , Protein Binding , SARS-CoV-2 , Spike Glycoprotein, CoronavirusABSTRACT
Correction for 'Antiviral drug design based on the opening mechanism of spike glycoprotein in SARS-CoV-2' by Ruichao Mao et al., Phys. Chem. Chem. Phys., 2021, DOI: 10.1039/d1cp01045j.
ABSTRACT
The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters the host cell after the receptor binding domain (RBD) of the virus spike (S) glycoprotein binds to the human angiotensin-converting enzyme 2 (hACE2). This binding requires the RBD to undergo a conformational change from a closed to an open state. In the present study, a key pair of salt bridges formed by the side chains of K537 and E619, residues at the interfaces of SD1 and SD2, respectively, was identified to promote the opening of the RBD. Mutations of K537Q and E619D reduced their side chain lengths and eliminated this pair of salt bridges; as a result, the opening of the RBD was not observed in the MD simulations. Thus, blocking the formation of this pair of salt bridges is a promising approach for treating novel coronavirus disease 2019 (COVID-19). FDA approved drug molecules were screened by their capabilities of blocking the formation of the key pair of salt bridges, achieved by their positional stabilities in the cavity containing the side chains of K537 and E619 formed in the interface between SD1 and SD2. Simeprevir, imatinib, and naldemedine were identified to possess the desired capability with the most favorable interaction energies.