Potential inhibitors for blocking the interaction of the coronavirus SARS-CoV-2 spike protein and its host cell receptor ACE2
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Abstract
Background
The outbreak of SARS-CoV-2 continues to pose a serious threat to human health and social. The ongoing pandemic of COVID-19 caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has made a serious threat to public health and economic stability worldwide. Given the urgency of the situation, researchers are attempting to repurpose existing drugs for treating COVID-19.
Methods
We first established an anti-coronavirus drug screening platform based on the Homogeneous Time Resolved Fluorescence (HTRF) technology and the interaction between the coronavirus spike protein and its host receptor ACE2. Two compound libraries of 2,864 molecules were screened with this platform. Selected candidate compounds were validated by SARS-CoV-2_S pseudotyped lentivirus and ACE2-overexpressing cell system. Molecular docking was used to analyze the interaction between S protein and compounds.
Results
We identified three potential anti-coronavirus compounds: tannic acid (TA), TS-1276 (anthraquinone), and TS-984 (9-Methoxycanthin-6-one). Our in vitro validation experiments indicated that TS-984 strongly inhibits the interaction of the coronavirus S protein and the human cell ACE2 receptor. Additionally, tannic acid showed moderate inhibitory effect on the interaction of S protein and ACE2.
Conclusion
This platform is a rapid, sensitive, specific, and high throughput system, and available for screening large compound libraries. TS-984 is a potent blocker of the interaction between the S-protein and ACE2, which might have the potential to be developed into an effective anti-coronavirus drug.
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SciScore for 10.1101/2021.12.14.472545: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics not detected. Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources TA was purchased from the United States of America. TAsuggested: RRID:CVCL_4315)Experimental cell lines and reagents: Cell lines: ACE2-overexpressing 293T cells (with mCherry labeled vector), 293T cells (only vector overexpressed), ACE2-overexpressing Capan2 cells (mCherry labeled vector), Capan2 cells (only vector overexpressed), were all donated from Chaonan Qian’s laboratory (SYSUCC, Guangzhou, China). 293Tsuggested: NonePseudovirus neutralization assay on … SciScore for 10.1101/2021.12.14.472545: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics not detected. Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources TA was purchased from the United States of America. TAsuggested: RRID:CVCL_4315)Experimental cell lines and reagents: Cell lines: ACE2-overexpressing 293T cells (with mCherry labeled vector), 293T cells (only vector overexpressed), ACE2-overexpressing Capan2 cells (mCherry labeled vector), Capan2 cells (only vector overexpressed), were all donated from Chaonan Qian’s laboratory (SYSUCC, Guangzhou, China). 293Tsuggested: NonePseudovirus neutralization assay on ACE2-overexpressing pancreatic carcinoma cell line Capan2: One day before SARS-CoV-2 pseudovirus transduction (Day 0), Capan2 cells were washed once with D-PBS and dissociated using 0.25% of Trypsin. Capan2suggested: CLS Cat# 300144/p660_Capan-2, RRID:CVCL_0026)Software and Algorithms Sentences Resources The docking of TS-984 and the S protein/ACE2 complex was completed with the software Autodock 4.0 [23]. Autodocksuggested: (AutoDock, RRID:SCR_012746)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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