Molecular docking between human TMPRSS2 and the serine protease Kunitz-type inhibitor rBmTI-A
This article has been Reviewed by the following groups
Listed in
- Evaluated articles (ScreenIT)
Abstract
SARS-CoV-2 entrance into host cells is dependent of ACE2 receptor and viral protein S initiation by serine protease TMPRSS2. Cleavage of coronavirus protein S at the junctions Arg685/Ser686 and Arg815/Ser816 leads to the production of the S1/S2 and S2’ fragments needed for the fusion of viral and cell membranes. Studying and identifying serine protease inhibitors is an important step towards the development of candidate drugs to prevent SARS-CoV-2 infection. It has already been stablished that camostat mesylate, a serine protease inhibitor, is capable of blocking TMPRSS2 activity and prevent SARS-CoV-2 entrance into host cells. In this work, the interaction between the two domains of Kunitz-type serine protease inhibitor rBmTI-A and TMPRSS2 was studied through molecular docking. rBmTI-A domain 2 (P1 site Leu84) had the best complex results with predicted binding affinity of -12 Kcal.mol -1 and predicted dissociation constant at 25°C of 1.6 nM. The results suggest that rBmTI-A is capable of binding TMPRSS2 cleavage site at the junction Arg815/Ser816 using essentially the same residues that camostat mesylate.
Article activity feed
-
SciScore for 10.1101/2022.03.13.484191: (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. Table 2: Resources
Software and Algorithms Sentences Resources 1.0 [35] and Ligplot+ v.2.2 [36] were used to assess binding affinity energy and different types of interactions. Ligplot+suggested: (LigPlot+, RRID:SCR_018249)2.4.1 (The PyMOL Molecular Graphics System, Version 2.0 Schrödinger, LLC) and VMD v. PyMOLsuggested: (PyMOL, RRID:SCR_000305)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 …SciScore for 10.1101/2022.03.13.484191: (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. Table 2: Resources
Software and Algorithms Sentences Resources 1.0 [35] and Ligplot+ v.2.2 [36] were used to assess binding affinity energy and different types of interactions. Ligplot+suggested: (LigPlot+, RRID:SCR_018249)2.4.1 (The PyMOL Molecular Graphics System, Version 2.0 Schrödinger, LLC) and VMD v. PyMOLsuggested: (PyMOL, RRID:SCR_000305)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 did not find any issues relating to the usage of bar graphs.
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.
- No funding statement was detected.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
-
