INT341086

Context Info Confidence 0.13 First Reported 2010 Last Reported 2010 Negated 0 Speculated 1 Reported most in Body Documents 1 Total Number 8 Disease Relevance 1.12 Pain Relevance 0.09

HRC (Homo sapiens)

Pain Link Frequency Relevance Heat Potency 40 99.80 isoflurane 16 5.00 Central nervous system 8 5.00 anesthesia 8 5.00 medulla 8 5.00

Disease Link Frequency Relevance Heat Parainfluenza Virus Infection 32 92.88 Henipavirus Infections 8 81.56 Acquired Immune Deficiency Syndrome Or Hiv Infection 40 77.76 Infection 392 76.04 Respiratory Syncytial Virus 56 71.80 Measles 32 71.40 Disease 120 67.04 Viral Meningitis 88 58.00 Lifespan 8 57.04 Neurological Disease 16 42.80

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Mutation

Event

Anatomy

Negation

Speculation

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Disease term

The data reported in this manuscript however suggest that if HRC peptides are localized to the cell membrane by a cholesterol tag, and are engineered to interact more strongly with the HRN target domain, they become capable of interacting with F prior to the insertion of the fusion peptide into the target cell membrane.

HRC Binding (interact) of

1) Confidence 0.13 Published 2010 Journal PLoS Pathogens Section Body Doc Link PMC2965769 Disease Relevance 0.45 Pain Relevance 0

To explain the greater stability of the heterologous pair, we expanded on our previous residue-by residue evaluation of the HRN-HRC interaction, and studied this interaction in atomic detail.

HRN-HRC Binding (interaction) of

2) Confidence 0.13 Published 2010 Journal PLoS Pathogens Section Body Doc Link PMC2965769 Disease Relevance 0.08 Pain Relevance 0

Our results provide strong evidence that interhelical packing interactions in the F ectodomain core are important determinants of the stability of HRN-HRC interaction, and thus of peptide inhibitor activity.

HRN-HRC Binding (interaction) of

3) Confidence 0.13 Published 2010 Journal PLoS Pathogens Section Body Doc Link PMC2965769 Disease Relevance 0 Pain Relevance 0

HPIV3 HRC peptides act by binding to the F HRN coiled coil, disrupting postfusion six-helix bundle (6HB) formation and blocking viral entry.

HRC Binding (binding) of

4) Confidence 0.11 Published 2010 Journal PLoS Pathogens Section Body Doc Link PMC2965769 Disease Relevance 0.15 Pain Relevance 0

Note that all peptides bear the Glu459-to-Val mutation that we previously identified as enhancing HRN-HRC interaction and potency [48].

HRN-HRC Binding (interaction) of associated with potency

5) Confidence 0.11 Published 2010 Journal PLoS Pathogens Section Body Doc Link PMC2965769 Disease Relevance 0 Pain Relevance 0.05

The current paradigm for the mechanism of HR-derived peptide action proposes that HRC peptides bind to the postulated extended intermediate state, after the fusion peptide has inserted into the target membrane, and prevent the transition to the post-fusion conformation [5], [44], [45].

HRC Spec (postulated) Binding (bind) of

6) Confidence 0.08 Published 2010 Journal PLoS Pathogens Section Body Doc Link PMC2965769 Disease Relevance 0.22 Pain Relevance 0.04

In this work, we report that unlike the untagged HRC peptides, which bind to the postulated extended intermediate state bridging the viral and cell membranes, the cholesterol tagged HRC-derived peptides interact with F before the fusion peptide inserts into the target cell membrane, thus capturing an earlier stage in the F-activation process.

HRC Binding (bind) of

7) Confidence 0.08 Published 2010 Journal PLoS Pathogens Section Abstract Doc Link PMC2965769 Disease Relevance 0.13 Pain Relevance 0

The basis for this phenomenon lies in the greater stability of the interaction between the heterologous HRN-HRC pair (NiV-HPIV3) compared to the homologous pair (NiV-NiV) [48].

HRN-HRC Binding (interaction) of

8) Confidence 0.08 Published 2010 Journal PLoS Pathogens Section Body Doc Link PMC2965769 Disease Relevance 0.08 Pain Relevance 0

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