Molecular dynamics analysis predicts ritonavir and naloxegol strongly block the SARS-CoV-2 spike protein-hACE2 binding

  title={Molecular dynamics analysis predicts ritonavir and naloxegol strongly block the SARS-CoV-2 spike protein-hACE2 binding},
  author={Milad Bagheri and Ahmadreza Niavarani},
  journal={Journal of Biomolecular Structure and Dynamics},
  pages={1597 - 1606}
  • M. Bagheri, A. Niavarani
  • Published 8 October 2020
  • Chemistry, Biology
  • Journal of Biomolecular Structure and Dynamics
Abstract The rapid emergence of COVID-19 pandemics has posed humans particularly vulnerable to the novel SARS-CoV-2 virus. Since de novo drug discovery is both expensive and time-consuming, drug repurposing approaches are believed to be of particular help. The SARS-CoV-2 spike (S) protein is known to attach human angiotensin-converting enzyme-2 (hACE2) through its receptor-binding domain (RBD). We screened 1930 FDA-approved ligands for the selection of optimal ones blocking this interaction… 
In silico drug repositioning against human NRP1 to block SARS-CoV-2 host entry
  • Şeref Gül
  • Biology, Chemistry
    Turkish Journal of Biology
  • 2021
Structural information of the NRP1 in complex with C-terminal of spike (S) protein of SARS-CoV-2 is taken advantage to identify drugs that may inhibit N RP1 and S protein interaction and validate the effect of drugs analyzed by experimental studies and clinical trials will expedite the drug discovery process for COVID-19.
A Repurposed Drug Screen Identifies Compounds That Inhibit the Binding of the COVID-19 Spike Protein to ACE2
The best candidates were Thiostrepton, Oxytocin, Nilotinib, and Hydroxycamptothecin with IC50’s in the 4–9 μM range, and these results highlight an effective screening approach to identify compounds capable of disrupting the Spike-ACE2 interaction.
Macrolides May Prevent Severe Acute Respiratory Syndrome Coronavirus 2 Entry into Cells: A Quantitative Structure Activity Relationship Study and Experimental Validation
Three macrolide antibiotics display a narrow antiviral activity window against SARS-CoV-2, and it may be of interest to further investigate their effect on the viral spike protein and their potential in combination therapies for the coronavirus disease 19 early stage of infection.
Disruption of disulfides within RBD of SARS‐CoV‐2 spike protein prevents fusion and represents a target for viral entry inhibition by registered drugs
It is demonstrated that the integrity of disulfide bonds within the receptor‐binding domain (RBD) plays an important role in the membrane fusion process although their disruption does not prevent binding of spike protein to ACE2.


Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2
Cryo–electron microscopy structures of full-length human ACE2 in the presence of the neutral amino acid transporter B0AT1 with or without the receptor binding domain (RBD) of the surface spike glycoprotein of SARS-CoV-2 are presented, providing important insights into the molecular basis for coronavirus recognition and infection.
Structure of MERS-CoV spike receptor-binding domain complexed with human receptor DPP4
The atomic details at the interface between MERS-CoV RBD and DPP4 provide structural understanding of the virus and receptor interaction, which can guide development of therapeutics and vaccines against MERS -CoV infection.
Structural Basis for Potent Neutralization of Betacoronaviruses by Single-domain Camelid Antibodies
The isolation and characterization of single-domain antibodies (VHHs) from a llama immunized with prefusion-stabilized coronavirus spikes are described and a molecular basis for the neutralization of pathogenic betacoronaviruses by VHHs is provided and it is suggested that these molecules may serve as useful therapeutics during coronav virus outbreaks.
Cross-neutralization of SARS-CoV-2 by a human monoclonal SARS-CoV antibody
Several monoclonal antibodies that target the S glycoprotein of SARS-CoV-2, which was identified from memory B cells of an individual who was infected with severe acute respiratory syndrome coronavirus (SARS- coV) in 2003, and one antibody (named S309) potently neutralization, which may limit the emergence of neutralization-escape mutants.
Pharmacokinetics of Lopinavir and Ritonavir in Patients Hospitalized With Coronavirus Disease 2019 (COVID-19)
T trough levels of lopinavir and ritonavir are quantified by liquid chromatography–tandem mass spectrometry in patients admitted to a “normal care” ward because of COVID-19, finding that steady-state conditions may be assumed for all patients.
Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation
The authors show that this protein binds at least 10 times more tightly than the corresponding spike protein of severe acute respiratory syndrome (SARS)–CoV to their common host cell receptor, and test several published SARS-CoV RBD-specific monoclonal antibodies found that they do not have appreciable binding to 2019-nCoV S, suggesting that antibody cross-reactivity may be limited between the two RBDs.