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Neuraminidase 1 and 2 Active Site Comparison for Viral Drug Resistance Analysis
Author(s) -
Sieradzki Guinevere,
Mierswa Sabrina,
Sabin Amber,
DeBruine Anna,
Koprek Jessica,
Perez Victoria,
Minx Connor,
Persaud Krishna,
Selvik Josephine,
Smith Behrgen,
Zieman Joshua,
Kanungo Muskan,
Berkowicz Alexandra,
Cabrera-Brito Bella,
Pung Benjamin,
Alexander Anne
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.04487
Subject(s) - active site , neuraminidase , protein data bank (rcsb pdb) , oseltamivir , neuraminidase inhibitor , virtual screening , drug , drug resistance , computational biology , virology , biology , chemistry , drug discovery , medicine , virus , stereochemistry , biochemistry , pharmacology , enzyme , genetics , infectious disease (medical specialty) , covid-19 , disease , pathology
Neuraminidase is an important protein on the surface of influenza and is an antiviral target. There are several types of neuraminidase, but this project focuses on neuraminidase 1 (N1) and 2 (N2) because of their prevalence in human influenza A infections. The amino acid residues in the active sites of N1 and N2 are 94% identical. However, there are several key differences that affect how N1 and N2 interact with the same antiviral drug. The purpose of this project is to gain a deeper understanding of viral drug resistance by modeling the active sites of N1 and N2 and their interactions with oseltamivir (Tamiflu). Two PDB files have been selected for N1 (2HU4) and N2 (4GZP). These PDB files will initially be overlaid in Jmol to identify the level of structural similarity, then active site boxes will be 3D printed for N1 and N2. Active site boxes model only the active site of a molecule, giving a detailed view and understanding of this specific location. Within the models for N1 and N2, Jmol will be used to highlight amino acids E276, I222, and H274Y to investigate their effects on inhibitor interactions. Additionally, a model of the inhibitor oseltamivir (Tamiflu) will be 3D printed to compare its interactions with N1 and N2. These active site boxes will enhance the scientific education and study of these active sites. Support or Funding Information This work is part of the CREST program, supported by National Science Foundation Grants I022793, I323414, and 172s940.