Design of Potent Membrane Fusion Inhibitors against SARS-CoV-2, an Emerging Coronavirus with High Fusogenic Activity
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Abstract
The COVID-19 pandemic, caused by SARS-CoV-2, presents a serious global public health emergency in urgent need of prophylactic and therapeutic interventions. The S protein of coronaviruses mediates viral receptor binding and membrane fusion, thus being considered a critical target for antivirals. Herein, we report that the SARS-CoV-2 S protein has evolved a high level of activity to mediate cell-cell fusion, significantly differing from the S protein of SARS-CoV that emerged previously. The HR1 sequence in the fusion protein of SARS-CoV-2 adopts a much higher helical stability than the HR1 sequence in the fusion protein of SARS-CoV and can interact with the HR2 site to form a six-helical bundle structure more efficiently, underlying the mechanism of the enhanced fusion capacity. Also, importantly, the design of membrane fusion inhibitors with high potencies against both SARS-CoV-2 and SARS-CoV has provided potential arsenals to combat the pandemic and tools to exploit the fusion mechanism.
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SciScore for 10.1101/2020.03.26.009233: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources Single-cycle infection assay: Infectivity of SARS-CoV-2, SARS-CoV, and vesicular stomatitis virus (VSV) on 293T cells or 293T cells stably expressing human ACE2 (293T/ACE2) was determined by a single-cycle infection assay as described previously (60). 293Tsuggested: NoneTo produce pseudoviruses, HEK293T cells were cotransfected with a backbone plasmid (pNL4-3.luc. HEK293Tsuggested: NoneThe mixture was then added to 293T/ACE2 cells at a … SciScore for 10.1101/2020.03.26.009233: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources Single-cycle infection assay: Infectivity of SARS-CoV-2, SARS-CoV, and vesicular stomatitis virus (VSV) on 293T cells or 293T cells stably expressing human ACE2 (293T/ACE2) was determined by a single-cycle infection assay as described previously (60). 293Tsuggested: NoneTo produce pseudoviruses, HEK293T cells were cotransfected with a backbone plasmid (pNL4-3.luc. HEK293Tsuggested: NoneThe mixture was then added to 293T/ACE2 cells at a density of 104 cells/100 μl per plate well. 293T/ACE2suggested: RRID:CVCL_YZ65)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:- No conflict of interest statement was detected. If there are no conflicts, we encourage authors to explicit state so.
- 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.
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