ArticleInternational journal of antimicrobial agents2020
Synergistic antiviral effect of hydroxychloroquine and azithromycin in combination against SARS-CoV-2: What molecular dynamics studies of virus-host interactions reveal.
Article in International journal of antimicrobial agents, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed, 117 citations in OpenAlex.
- Azithromycin and hydroxychloroquine in hospitalised patients with confirmed COVID-19: a randomised double-blinded placebo-controlled trial.The European respiratory journal · 2022Trial
- Effect of Hydroxychloroquine in Hospitalized Patients with Covid-19.The New England journal of medicine · 2020Trial
- The Enigmatic Conserved Q134-F135-N137 Triad in SARS-CoV-2 Spike Protein: A Conformational Transducer?Biomolecules · 2026Review
- Article
- Current development of severe acute respiratory syndrome coronavirus 2 neutralizing antibodies (Review).Molecular medicine reports · 2024Review
- Single-molecule imaging reveals allosteric stimulation of SARS-CoV-2 spike receptor binding domain by host sialic acid.Science advances · 2024Article
- Review
- Treating diabetes with combination of phosphodiesterase 5 inhibitors and hydroxychloroquine-a possible prevention strategy for COVID-19?Molecular and cellular biochemistry · 2023Review
- Identification of possible binding modes of SARS-CoV-2 spikeChemical physics letters · 2023Article
- Role of cholesterol-recognition motifs in the infectivity of SARS-CoV-2 variants.Colloids and surfaces. B, Biointerfaces · 2023Article
- Review
- Convergent Evolution Dynamics of SARS-CoV-2 and HIV Surface Envelope Glycoproteins Driven by Host Cell Surface Receptors and Lipid Rafts: Lessons for the Future.International journal of molecular sciences · 2023Review
- A Vaccine Strategy Based on the Identification of an Annular Ganglioside Binding Motif in Monkeypox Virus Protein E8L.Viruses · 2022Article
- Article
- Bacterial infection in coronavirus disease 2019 patients: co-infection, super-infection and how it impacts on antimicrobial use.Current opinion in critical care · 2022Review
- Molecular dynamics studies reveal structural and functional features of the SARS-CoV-2 spike protein.BioEssays : news and reviews in molecular, cellular and developmental biology · 2022Review
- Molecular landscape of BoNT/B bound to a membrane-inserted synaptotagmin/ganglioside complex.Cellular and molecular life sciences : CMLS · 2022Article
- Methodology-Centered Review of Molecular Modeling, Simulation, and Prediction of SARS-CoV-2.Chemical reviews · 2022Review
- Structural Dynamics of the SARS-CoV-2 Spike Protein: A 2-Year Retrospective Analysis of SARS-CoV-2 Variants (from Alpha to Omicron) Reveals an Early Divergence between Conserved and Variable Epitopes.Molecules (Basel, Switzerland) · 2022Article
- Skeletal Muscle and COVID-19: The Potential Involvement of Bioactive Sphingolipids.Biomedicines · 2022Review
4 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The emergence of SARS-coronavirus-2 (SARS-CoV-2) has led to a global pandemic disease referred to as coronavirus disease 19 (COVID-19). Hydroxychloroquine (CLQ-OH)/azithromycin (ATM) combination therapy is currently being tested for the treatment of COVID-19, with promising results. However, the molecular mechanism of action of this combination is not yet established. Using molecular dynamics (MD) simulations, this study shows that the drugs act in synergy to prevent any close contact between the virus and the plasma membrane of host cells. Unexpected molecular similarity is shown between ATM and the sugar moiety of GM1, a lipid raft ganglioside acting as a host attachment cofactor for respiratory viruses. Due to this mimicry, ATM interacts with the ganglioside-binding domain of SARS-CoV-2 spike protein. This binding site shared by ATM and GM1 displays a conserved amino acid triad Q-134/F-135/N-137 located at the tip of the spike protein. CLQ-OH molecules are shown to saturate virus attachment sites on gangliosides in the vicinity of the primary coronavirus receptor, angiotensin-converting enzyme-2 (ACE-2). Taken together, these data show that ATM is directed against the virus, whereas CLQ-OH is directed against cellular attachment cofactors. We conclude that both drugs act as competitive inhibitors of SARS-CoV-2 attachment to the host-cell membrane. This is consistent with a synergistic antiviral mechanism at the plasma membrane level, where therapeutic intervention is likely to be most efficient. This molecular mechanism may explain the beneficial effects of CLQ-OH/ATM combination therapy in patients with COVID-19. Incidentally, the data also indicate that the conserved Q-134/F-135/N-137 triad could be considered as a target for vaccine strategies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.