Homology Modeling and Analysis of Structure Predictions of the Bovine Rhinitis B Virus RNA Dependent RNA Polymerase (RdRp)
Overview
Chemistry
Molecular Biology
Authors
Affiliations
Bovine Rhinitis B Virus (BRBV) is a picornavirus responsible for mild respiratory infection of cattle. It is probably the least characterized among the aphthoviruses. BRBV is the closest relative known to Foot and Mouth Disease virus (FMDV) with a ~43% identical polyprotein sequence and as much as 67% identical sequence for the RNA dependent RNA polymerase (RdRp), which is also known as 3D polymerase (3D(pol)). In the present study we carried out phylogenetic analysis, structure based sequence alignment and prediction of three-dimensional structure of BRBV 3D(pol) using a combination of different computational tools. Model structures of BRBV 3D(pol) were verified for their stereochemical quality and accuracy. The BRBV 3D(pol) structure predicted by SWISS-MODEL exhibited highest scores in terms of stereochemical quality and accuracy, which were in the range of 2Å resolution crystal structures. The active site, nucleic acid binding site and overall structure were observed to be in agreement with the crystal structure of unliganded as well as template/primer (T/P), nucleotide tri-phosphate (NTP) and pyrophosphate (PPi) bound FMDV 3D(pol) (PDB, 1U09 and 2E9Z). The closest proximity of BRBV and FMDV 3D(pol) as compared to human rhinovirus type 16 (HRV-16) and rabbit hemorrhagic disease virus (RHDV) 3D(pols) is also substantiated by phylogeny analysis and root-mean square deviation (RMSD) between C-α traces of the polymerase structures. The absence of positively charged α-helix at C terminal, significant differences in non-covalent interactions especially salt bridges and CH-pi interactions around T/P channel of BRBV 3D(pol) compared to FMDV 3D(pol), indicate that despite a very high homology to FMDV 3D(pol), BRBV 3D(pol) may adopt a different mechanism for handling its substrates and adapting to physiological requirements. Our findings will be valuable in the design of structure-function interventions and identification of molecular targets for drug design applicable to Aphthovirus RdRps.
Tripathi Y, Singh V, Kumar S, Shukla V, Yadav M, Upadhyay R BMC Microbiol. 2024; 24(1):336.
PMID: 39256659 PMC: 11389467. DOI: 10.1186/s12866-024-03434-x.
Discovery and characterization of BRBV-sheep virus in nasal swabs from domestic sheep in China.
Zhang Y, Li Y, Qi L, Hang T, Wang P, Wang Y Front Cell Infect Microbiol. 2024; 14:1380708.
PMID: 39006745 PMC: 11239340. DOI: 10.3389/fcimb.2024.1380708.
Amjad H, Saleem F, Ahmad M, Nisar U, Arshad Dar H Food Chem (Oxf). 2024; 8:100191.
PMID: 38259869 PMC: 10801198. DOI: 10.1016/j.fochms.2023.100191.
Detection and Genomic Characterization of Bovine Rhinitis Virus in China.
Zhou Y, Chen X, Tang C, Yue H Animals (Basel). 2023; 13(2).
PMID: 36670851 PMC: 9854767. DOI: 10.3390/ani13020312.
CoVM: Molecular Biological Data Integration of SARS-CoV-2 Proteins in a Macro-to-Micro Method.
Chen H, Hu X, Hu Y, Zhou J, Chen M Biomolecules. 2022; 12(8).
PMID: 36008961 PMC: 9405999. DOI: 10.3390/biom12081067.