A fusion protein’s weak link: functional constraints revealed by inhibitory peptide interaction with the parainfluenza fusion protein

Human parainfluenza viruses (HPIVs) cause significant respiratory illnesses including croup and pneumonia. HPIV infection begins with fusion of viral and host cell membranes, driven by the coordinated actions of the attachment (HN) and fusion (F) glycoproteins, which together form the fusion/entry complex. We have described fusion inhibitory peptides derived from the heptad repeat (HRC) domain of the F glycoprotein with potent antiviral activity against HPIV3 and other paramyxoviruses. These peptides inhibit fusion by binding to the transiently exposed N-terminal heptad repeat (HRN) segments of the F prehairpin intermediate and preventing the six-helix bundle (6HB) formation that is required for the membrane fusion process. We report viral variants that escape inhibition by an α/β-substituted HRC peptide of HPIV3 through an HN mutation that enhances HN’s activation of F, and a mutation in F’s HRN domain that destabilizes the 6HB. The F HRN domain bearing the alteration shows reduced α-h..., , # Data from: A fusion protein’s weak link: functional constraints revealed by inhibitory peptide interaction with the parainfluenza fusion protein

### Dryad_Repository_for_S164P_final_annotated.xlsx
In `Dryad_Repository_for_S164P_final_annotated.xlsx` and `Dryad_Repository_for_S164P_final_no_formating.xlsx`, each tab contains raw data and is named according to the figure panels used in the manuscript: A fusion protein’s weak link: functional constraints revealed by inhibitory peptide interaction with the parainfluenza fusion protein. The first worksheet in each file describes the figures. The content for both files is the same: one contains formatting for readability, and the other does not.

**Abbreviations:**

* HN: hemagglutinin-neuraminidase protein
* F: fusion protein
* HA: uncleaved influenza hemagglutinin
* Parental: clinical isolate HPIV3 virus bearing the HN H552Q mutation used as the input virus for viral evolution.
* VI-8-EV: virus bearing the HN N556D and F S164P mutations..., ,