ArticleInformatics in medicine unlocked2020
Leaving no stone unturned: Allosteric targeting of SARS-CoV-2 spike protein at putative druggable sites disrupts human angiotensin-converting enzyme interactions at the receptor binding domain.
Article in Informatics in medicine unlocked, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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The trial behind it
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Who cites it
12 citing papers in PubMed, 23 citations in OpenAlex.
- Review
- Identifying promising druggable binding sites and their flexibility to target the receptor-binding domain of SARS-CoV-2 spike protein.Computational and structural biotechnology journal · 2023Article
- Article
- An Evolutionary Conservation and Druggability Analysis of Enzymes Belonging to the Bacterial Shikimate Pathway.Antibiotics (Basel, Switzerland) · 2022Article
- Inhibition of ACE2-Spike Interaction by an ACE2 Binder Suppresses SARS-CoV-2 Entry.Angewandte Chemie (International ed. in English) · 2022Article
- Contributions of single-particle cryoelectron microscopy toward fighting COVID-19.Trends in biochemical sciences · 2022Review
- Structure based Drug Designing Approaches in SARS-CoV-2 Spike Inhibitor Design.Current topics in medicinal chemistry · 2022Review
- Distant residues modulate conformational opening in SARS-CoV-2 spike protein.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- More Is Always Better Than One: The N-Terminal Domain of the Spike Protein as Another Emerging Target for Hampering the SARS-CoV-2 Attachment to Host Cells.International journal of molecular sciences · 2021Article
- The impact of structural bioinformatics tools and resources on SARS-CoV-2 research and therapeutic strategies.Briefings in bioinformatics · 2021Review
- Discovery of Small-Molecule Inhibitors of SARS-CoV-2 Proteins Using a Computational and Experimental Pipeline.Frontiers in molecular biosciences · 2021Article
- A Repurposed Drug Screen Identifies Compounds That Inhibit the Binding of the COVID-19 Spike Protein to ACE2.Frontiers in pharmacology · 2021Article
Corrections and comments
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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 systematic entry of SARS-CoV-2 into host cells, as mediated by its Spike (S) protein, is highly essential for pathogenicity in humans. Hence, targeting the viral entry mechanisms remains a major strategy for COVID-19 treatment. Although recent efforts have focused on the direct inhibition of S-protein receptor-binding domain (RBD) interactions with human angiotensin-converting enzyme 2 (hACE2), allosteric targeting remains an unexplored possibility. Therefore, in this study, for the first time, we employed an integrative meta-analytical approach to investigate the allosteric inhibitory mechanisms of SARS-CoV-2 S-protein and its association with hACE2. Findings revealed two druggable sites (Sites 1 and 2) located at the N-terminal domain (NTD) and S2 regions of the protein. Two high-affinity binders; ZINC3939013 (Fosaprepitant - Site 1) and ZINC27990463 (Lomitapide - Site 2) were discovered via site-directed high-throughput screening against a library of ~1500 FDA approved drugs. Interestingly, we observed that allosteric binding of both compounds perturbed the prefusion S-protein conformations, which in turn, resulted in unprecedented hACE2 displacement from the RBD. Estimated
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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.