SARS-CoV-2 Spike Glycoprotein and ACE2 interaction reveals modulation of viral entry in wild and domestic animals
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Abstract
Background
SARS-CoV-2 is a viral pathogen causing life-threatening disease in human. Interaction between spike protein of SARS-CoV-2 and ACE2 receptor on the cells is a potential factor in the infectivity of a host. The interaction of SARS-CoV-2 spike receptor-binding domain with its receptor - ACE2, in different hosts was evaluated to understand and predict viral entry. The protein and nucleotide sequences of ACE2 were initially compared across different species to identify key differences among them. The ACE2 receptor of various species was homology modeled (6LZG, 6M0J, and 6VW1 as a reference), and its binding ability to the spike ACE2 binding domain of SARS-CoV-2 was assessed. Initially, the spike binding parameters of ACE2 of known infected and uninfected species were compared with each Order (of animals) as a group. Finally, a logistic regression model vis-a-vis the spike binding parameters of ACE2 (considering data against 6LZG and 6M0J) was constructed to predict the probability of viral entry in different hosts.
Results
Phylogeny and alignment comparison did not lead to any meaningful conclusion on viral entry in different hosts. Out of several spike binding parameters of ACE2, a significant difference between the known infected and uninfected species was observed for six parameters. However, these parameters did not specifically categorize the Orders (of animals) into infected or uninfected. The logistic regression model constructed revealed that in the mammalian class, most of the species of Carnivores, Artiodactyls, Perissodactyls, Pholidota, and Primates had high probability of viral entry. However, among the primates, African Elephant had low probability of viral entry. Among rodents, hamsters were highly probable for viral entry with rats and mice having a medium to low probability. Rabbits have a high probability of viral entry. In Birds, ducks have a very low probability, while chickens seemed to have medium probability and turkey showed the highest probability of viral entry.
Conclusions
Most of the species considered in this study showed high probability of viral entry. This study would prompt us to closely follow certain species of animals for determining pathogenic insult by SARS-CoV-2 and for determining their ability to act as a carrier and/or disseminator.
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SciScore for 10.1101/2020.05.08.084327: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Software and Algorithms Sentences Resources Phylogenetic analysis: Phylogenetic analysis of the protein sequences was done using MEGA 6.0[38]. MEGAsuggested: (Mega BLAST, RRID:SCR_011920)The aligned sequences were then analyzed for the best nucleotide substitution model on the basis of Bayesian information criterion scores using the JModelTest software v2.1.7[40]. JModelTestsuggested: (jModelTest, RRID:SCR_015244)Homology modeling: The Structures of novel coronavirus spike receptor-binding domain complexed with its receptor - ACE2, that were determined through X-ray diffraction are available at PDB database with IDs 6LZG [25], 6M0J … SciScore for 10.1101/2020.05.08.084327: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Software and Algorithms Sentences Resources Phylogenetic analysis: Phylogenetic analysis of the protein sequences was done using MEGA 6.0[38]. MEGAsuggested: (Mega BLAST, RRID:SCR_011920)The aligned sequences were then analyzed for the best nucleotide substitution model on the basis of Bayesian information criterion scores using the JModelTest software v2.1.7[40]. JModelTestsuggested: (jModelTest, RRID:SCR_015244)Homology modeling: The Structures of novel coronavirus spike receptor-binding domain complexed with its receptor - ACE2, that were determined through X-ray diffraction are available at PDB database with IDs 6LZG [25], 6M0J [41] and 6VW1 [42]These available ACE2 models from PDB database were used for homology modeling using SWISS-MODEL[43], which was accessed through ExPASy web server. ExPASysuggested: NoneFive docked complexes were generated from GRAMM-X for each X-ray crystallography model in each species and post-docking analyses was carried out using Chimera software[46] and PRODIGY [47]. Chimerasuggested: (Chimera, RRID:SCR_002959)Further, in addition to delta G and RMSD, in FoldX software [48] several parameters were estimated for all these selected docked structures (for 432 models (48 hosts × 3 X-ray Crystallography models × 3 selected docking complexes) were analyzed), These parameters include - IntraclashesGroup1, IntraclashesGroup2 FoldXsuggested: (FoldX, RRID:SCR_008522)Results from OddPub: Thank you for sharing your data.
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.
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