Harnessing Endogenous Peptide Compounds as Potential Therapeutics for Severe Influenza
Abstract Background Excessive pulmonary inflammation and damage are characteristic features of severe influenza virus infections. LAT8881 is a synthetic 16–amino acid cyclic peptide form of a naturally occurring C-terminal fragment of human growth hormone with therapeutic efficacy against influenza....
Saved in:
| Published in: | The Journal of infectious diseases Vol. 230; no. 2; pp. e384 - e394 |
|---|---|
| Main Authors: | , , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
US
Oxford University Press
16.08.2024
|
| Subjects: | |
| ISSN: | 0022-1899, 1537-6613, 1537-6613 |
| Online Access: | Get full text |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Abstract | Abstract
Background
Excessive pulmonary inflammation and damage are characteristic features of severe influenza virus infections. LAT8881 is a synthetic 16–amino acid cyclic peptide form of a naturally occurring C-terminal fragment of human growth hormone with therapeutic efficacy against influenza. Shorter linear peptides are typically easier to manufacture and formulate for delivery than larger cyclic peptides. A 6–amino acid linear peptide fragment of LAT8881, LAT9997, was investigated as a potential influenza therapy.
Methods
LAT9997 was evaluated for its potential to limit disease in a preclinical mouse model of severe influenza infection.
Results
Intranasal treatment of mice with either LAT8881 or LAT9997 from day 1 following influenza infection significantly improved survival outcomes. Initiating LAT9997 treatment at the onset of severe disease also significantly improved disease severity. Greater disease resistance in LAT9997-treated mice correlated with reduced lung immunopathology, damage markers, vascular leak, and epithelial cell death. Treatment reduced viral loads, cytokines, and neutrophil infiltration in the airways yet maintained protective alveolar macrophages in a dose-dependent manner. Sequential trimming of N- and C-terminal amino acids from LAT9997 revealed a structure-activity relationship.
Conclusions
These findings provide preclinical evidence that therapeutic LAT9997 treatment limits viral burden and characteristic features of severe influenza, including hyperinflammation and lung damage.
Summary
Excessive pulmonary inflammation and damage are characteristic features of severe influenza virus infections. LAT9997 is a linear peptide fragment derived from human growth hormone. This study provides preclinical evidence that therapeutic LAT9997 treatment limits viral burden, hyperinflammation, and lung damage. |
|---|---|
| AbstractList | Abstract
Background
Excessive pulmonary inflammation and damage are characteristic features of severe influenza virus infections. LAT8881 is a synthetic 16–amino acid cyclic peptide form of a naturally occurring C-terminal fragment of human growth hormone with therapeutic efficacy against influenza. Shorter linear peptides are typically easier to manufacture and formulate for delivery than larger cyclic peptides. A 6–amino acid linear peptide fragment of LAT8881, LAT9997, was investigated as a potential influenza therapy.
Methods
LAT9997 was evaluated for its potential to limit disease in a preclinical mouse model of severe influenza infection.
Results
Intranasal treatment of mice with either LAT8881 or LAT9997 from day 1 following influenza infection significantly improved survival outcomes. Initiating LAT9997 treatment at the onset of severe disease also significantly improved disease severity. Greater disease resistance in LAT9997-treated mice correlated with reduced lung immunopathology, damage markers, vascular leak, and epithelial cell death. Treatment reduced viral loads, cytokines, and neutrophil infiltration in the airways yet maintained protective alveolar macrophages in a dose-dependent manner. Sequential trimming of N- and C-terminal amino acids from LAT9997 revealed a structure-activity relationship.
Conclusions
These findings provide preclinical evidence that therapeutic LAT9997 treatment limits viral burden and characteristic features of severe influenza, including hyperinflammation and lung damage.
Summary
Excessive pulmonary inflammation and damage are characteristic features of severe influenza virus infections. LAT9997 is a linear peptide fragment derived from human growth hormone. This study provides preclinical evidence that therapeutic LAT9997 treatment limits viral burden, hyperinflammation, and lung damage. Excessive pulmonary inflammation and damage are characteristic features of severe influenza virus infections. LAT8881 is a synthetic 16-amino acid cyclic peptide form of a naturally occurring C-terminal fragment of human growth hormone with therapeutic efficacy against influenza. Shorter linear peptides are typically easier to manufacture and formulate for delivery than larger cyclic peptides. A 6-amino acid linear peptide fragment of LAT8881, LAT9997, was investigated as a potential influenza therapy.BACKGROUNDExcessive pulmonary inflammation and damage are characteristic features of severe influenza virus infections. LAT8881 is a synthetic 16-amino acid cyclic peptide form of a naturally occurring C-terminal fragment of human growth hormone with therapeutic efficacy against influenza. Shorter linear peptides are typically easier to manufacture and formulate for delivery than larger cyclic peptides. A 6-amino acid linear peptide fragment of LAT8881, LAT9997, was investigated as a potential influenza therapy.LAT9997 was evaluated for its potential to limit disease in a preclinical mouse model of severe influenza infection.METHODSLAT9997 was evaluated for its potential to limit disease in a preclinical mouse model of severe influenza infection.Intranasal treatment of mice with either LAT8881 or LAT9997 from day 1 following influenza infection significantly improved survival outcomes. Initiating LAT9997 treatment at the onset of severe disease also significantly improved disease severity. Greater disease resistance in LAT9997-treated mice correlated with reduced lung immunopathology, damage markers, vascular leak, and epithelial cell death. Treatment reduced viral loads, cytokines, and neutrophil infiltration in the airways yet maintained protective alveolar macrophages in a dose-dependent manner. Sequential trimming of N- and C-terminal amino acids from LAT9997 revealed a structure-activity relationship.RESULTSIntranasal treatment of mice with either LAT8881 or LAT9997 from day 1 following influenza infection significantly improved survival outcomes. Initiating LAT9997 treatment at the onset of severe disease also significantly improved disease severity. Greater disease resistance in LAT9997-treated mice correlated with reduced lung immunopathology, damage markers, vascular leak, and epithelial cell death. Treatment reduced viral loads, cytokines, and neutrophil infiltration in the airways yet maintained protective alveolar macrophages in a dose-dependent manner. Sequential trimming of N- and C-terminal amino acids from LAT9997 revealed a structure-activity relationship.These findings provide preclinical evidence that therapeutic LAT9997 treatment limits viral burden and characteristic features of severe influenza, including hyperinflammation and lung damage.CONCLUSIONSThese findings provide preclinical evidence that therapeutic LAT9997 treatment limits viral burden and characteristic features of severe influenza, including hyperinflammation and lung damage.Excessive pulmonary inflammation and damage are characteristic features of severe influenza virus infections. LAT9997 is a linear peptide fragment derived from human growth hormone. This study provides preclinical evidence that therapeutic LAT9997 treatment limits viral burden, hyperinflammation, and lung damage.SUMMARYExcessive pulmonary inflammation and damage are characteristic features of severe influenza virus infections. LAT9997 is a linear peptide fragment derived from human growth hormone. This study provides preclinical evidence that therapeutic LAT9997 treatment limits viral burden, hyperinflammation, and lung damage. Excessive pulmonary inflammation and damage are characteristic features of severe influenza virus infections. LAT8881 is a synthetic, 16 amino acid cyclic peptide form of a naturally occurring C-terminal fragment of human growth hormone with therapeutic efficacy against influenza. Shorter, linear peptides are typically easier to manufacture and formulate for delivery than larger cyclic peptides. A 6 amino acid linear peptide fragment of LAT8881, LAT9997, was investigated as a potential influenza therapy. LAT9997 was evaluated for its potential to limit disease in a preclinical mouse model of severe influenza infection. Intranasal treatment of mice with either LAT8881 or LAT9997 from day 1 following influenza infection significantly improved survival outcomes. Initiating LAT9997 treatment at the onset of severe disease, also significantly improved disease severity. Greater disease resistance in LAT9997-treated mice correlated with reduced lung immunopathology, damage markers, vascular leak, and epithelial cell death. Treatment reduced viral loads, cytokines, and neutrophil infiltration in the airways, yet maintained protective alveolar macrophages in a dose-dependent manner. Sequential trimming of N- and C-terminal amino acids from LAT9997 revealed a structure-activity relationship. These findings provide preclinical evidence that therapeutic LAT9997 treatment limits viral burden and characteristic features of severe influenza, including hyperinflammation and lung damage. |
| Author | Le Page, Mélanie A Harpur, Christopher M Hodges, Christopher West, Alison C Tate, Michelle D Gearing, Andrew J Ely, Lauren K Lam, Maggie |
| Author_xml | – sequence: 1 givenname: Alison C surname: West fullname: West, Alison C – sequence: 2 givenname: Christopher M surname: Harpur fullname: Harpur, Christopher M – sequence: 3 givenname: Mélanie A surname: Le Page fullname: Le Page, Mélanie A – sequence: 4 givenname: Maggie surname: Lam fullname: Lam, Maggie – sequence: 5 givenname: Christopher surname: Hodges fullname: Hodges, Christopher – sequence: 6 givenname: Lauren K surname: Ely fullname: Ely, Lauren K – sequence: 7 givenname: Andrew J surname: Gearing fullname: Gearing, Andrew J – sequence: 8 givenname: Michelle D orcidid: 0000-0002-0587-5514 surname: Tate fullname: Tate, Michelle D email: michelle.tate@hudson.org.au |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/38060822$$D View this record in MEDLINE/PubMed |
| BookMark | eNo9kM1LwzAYxoNM3IdePUqOeqjLR5s0RxnTDQQFp9eSNm9mRpfUphX0r7ey6emF5_3xwPObopEPHhC6pOSWEsXnzlvj4nzntMmEOEETmnGZCEH5CE0IYSyhuVJjNI1xRwhJuZBnaMxzIkjO2AS9rXTrIUbnt3jpTdiCD33Ez9B0zgBehH0Tem8i1kMYOvCd0zXevEOrG-g7V0VsQ4tf4BNawGtv6x78tz5Hp1bXES6Od4Ze75ebxSp5fHpYL-4ekyrNeJdYwaEqmcxSLimUFChNhWaKa6UMK3POcmlTYMoaAFmakhopDAGqLWMmBT5D14fepg0fPcSu2LtYQV1rD8OOginClKScsQG9OqJ9uQdTNK3b6_ar-HMxADcHIPTN_5eS4tdzcfBcHD3zHwQ8c0E |
| CitedBy_id | crossref_primary_10_1186_s12931_025_03192_y crossref_primary_10_1038_s41419_025_07748_0 |
| ContentType | Journal Article |
| Copyright | The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. 2023 The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. |
| Copyright_xml | – notice: The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. 2023 – notice: The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. |
| DBID | TOX NPM 7X8 |
| DOI | 10.1093/infdis/jiad566 |
| DatabaseName | Open Access: Oxford University Press Open Journals PubMed MEDLINE - Academic |
| DatabaseTitle | PubMed MEDLINE - Academic |
| DatabaseTitleList | MEDLINE - Academic PubMed |
| Database_xml | – sequence: 1 dbid: NPM name: PubMed url: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: TOX name: Open Access: Oxford University Press Open Journals url: https://academic.oup.com/journals/ sourceTypes: Publisher – sequence: 3 dbid: 7X8 name: MEDLINE - Academic url: https://search.proquest.com/medline sourceTypes: Aggregation Database |
| DeliveryMethod | fulltext_linktorsrc |
| Discipline | Medicine Biology |
| EISSN | 1537-6613 |
| EndPage | e394 |
| ExternalDocumentID | 38060822 10.1093/infdis/jiad566 |
| Genre | Journal Article |
| GroupedDBID | --- -DZ -~X ..I .2P .55 .GJ .I3 .XZ .ZR 08P 0R~ 123 1KJ 1TH 29K 2AX 2WC 36B 3O- 4.4 41~ 48X 53G 5GY 5RE 5VS 5WD 70D 85S AABZA AACGO AACZT AAHBH AAHTB AAJKP AAJQQ AAMVS AANCE AAOGV AAPGJ AAPNW AAPQZ AAPXW AAQQT AARHZ AAUAY AAUQX AAVAP AAWDT AAWTL AAYOK ABBHK ABDFA ABDPE ABEJV ABEUO ABGNP ABIXL ABJNI ABKDP ABLJU ABNHQ ABNKS ABOCM ABPEJ ABPLY ABPPZ ABPQP ABPTD ABQLI ABQNK ABSMQ ABTLG ABVGC ABWST ABXSQ ABXVV ABZBJ ACFRR ACGFO ACGFS ACGOD ACHIC ACPQN ACPRK ACUFI ACUTJ ACUTO ACVCV ACYHN ACZBC ADBBV ADEYI ADGZP ADHKW ADHZD ADIPN ADMTO ADNBA ADOCK ADQBN ADQXQ ADRTK ADULT ADVEK ADYVW ADZXQ AEGPL AEGXH AEJOX AEKPW AEKSI AEMDU AEMQT AENEX AENZO AEPUE AETBJ AEUPB AEWNT AEXZC AFFNX AFFQV AFFZL AFHKK AFIYH AFOFC AFQQW AFSHK AFXAL AFYAG AGINJ AGKEF AGKRT AGMDO AGQXC AGSYK AGUTN AHMBA AHMMS AHXPO AI. AIAGR AIJHB AJDVS AJEEA AJNCP ALMA_UNASSIGNED_HOLDINGS ALUQC ALXQX APIBT APJGH APWMN AQDSO AQKUS AQVQM ATGXG AVNTJ AXUDD BAWUL BAYMD BCRHZ BEYMZ BHONS BR6 BTRTY BVRKM BZKNY C45 CDBKE CS3 CZ4 D-I DAKXR DCCCD DIK DILTD DU5 D~K EBS ECGQY EE~ EIHJH EJD EMOBN ENERS F5P F9B FECEO FLUFQ FOEOM FOTVD FQBLK GAUVT GJXCC GX1 H13 H5~ HAR HQ3 HTVGU HW0 HZ~ IH2 IOX IPSME J21 J5H JAAYA JBMMH JENOY JHFFW JKQEH JLS JLXEF JPM JSG JST JXSIZ KAQDR KBUDW KOP KQ8 KSI KSN L7B LSO LU7 M49 MBLQV MHKGH MJL ML0 MVM N4W N9A NEJ NGC NOMLY NOYVH NU- NVLIB O0~ O9- OAUYM OAWHX OBFPC OCZFY ODMLO OJQWA OJZSN OK1 OPAEJ OVD OWPYF O~Y P0- P2P PAFKI PEELM PQQKQ Q1. Q5Y QBD RD5 ROX ROZ RUSNO RW1 RXO SA0 SJN TCURE TEORI TJX TMA TOX TR2 VH1 W2D W8F WH7 X7H X7M Y6R YAYTL YKOAZ YXANX ZE2 ZGI ZKG ZXP ~91 NPM 7X8 AHGBF AJBYB |
| ID | FETCH-LOGICAL-c453t-f63ecb2754371eb1e1146a293a99d2b83287f4e29fdee7bdb1d76d0e1af22d4e3 |
| IEDL.DBID | TOX |
| ISICitedReferencesCount | 3 |
| ISICitedReferencesURI | http://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestLinkType=CitingArticles&DestApp=WOS_CPL&KeyUT=001136424900001&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| ISSN | 0022-1899 1537-6613 |
| IngestDate | Sun Nov 09 11:37:59 EST 2025 Thu Apr 03 07:06:39 EDT 2025 Wed Apr 02 06:58:16 EDT 2025 |
| IsDoiOpenAccess | true |
| IsOpenAccess | true |
| IsPeerReviewed | true |
| IsScholarly | true |
| Issue | 2 |
| Keywords | cytokine influenza virus host-directed therapy pulmonary disease Influenza virus |
| Language | English |
| License | This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. |
| LinkModel | DirectLink |
| MergedId | FETCHMERGED-LOGICAL-c453t-f63ecb2754371eb1e1146a293a99d2b83287f4e29fdee7bdb1d76d0e1af22d4e3 |
| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
| ORCID | 0000-0002-0587-5514 |
| OpenAccessLink | https://dx.doi.org/10.1093/infdis/jiad566 |
| PMID | 38060822 |
| PQID | 2902971322 |
| PQPubID | 23479 |
| ParticipantIDs | proquest_miscellaneous_2902971322 pubmed_primary_38060822 oup_primary_10_1093_infdis_jiad566 |
| PublicationCentury | 2000 |
| PublicationDate | 20240816 |
| PublicationDateYYYYMMDD | 2024-08-16 |
| PublicationDate_xml | – month: 08 year: 2024 text: 20240816 day: 16 |
| PublicationDecade | 2020 |
| PublicationPlace | US |
| PublicationPlace_xml | – name: US – name: United States |
| PublicationTitle | The Journal of infectious diseases |
| PublicationTitleAlternate | J Infect Dis |
| PublicationYear | 2024 |
| Publisher | Oxford University Press |
| Publisher_xml | – name: Oxford University Press |
| SSID | ssj0004367 |
| Score | 2.4734135 |
| Snippet | Abstract
Background
Excessive pulmonary inflammation and damage are characteristic features of severe influenza virus infections. LAT8881 is a synthetic... Excessive pulmonary inflammation and damage are characteristic features of severe influenza virus infections. LAT8881 is a synthetic, 16 amino acid cyclic... Excessive pulmonary inflammation and damage are characteristic features of severe influenza virus infections. LAT8881 is a synthetic 16-amino acid cyclic... |
| SourceID | proquest pubmed oup |
| SourceType | Aggregation Database Index Database Publisher |
| StartPage | e384 |
| Title | Harnessing Endogenous Peptide Compounds as Potential Therapeutics for Severe Influenza |
| URI | https://www.ncbi.nlm.nih.gov/pubmed/38060822 https://www.proquest.com/docview/2902971322 |
| Volume | 230 |
| WOSCitedRecordID | wos001136424900001&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| hasFullText | 1 |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| link | http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwlV1LS8NAEB60qHjx_agvVvEaTHaTbPYoYtGDtWCV3sJmdwL1kEpTBf31znbTCupBLzkEsgnfDDOzmZ3vAzinTQ9PEGVgoxCDOClNUEhhAylEaQrj4qMXm5DdbjYYqF5DFl3_0sJX4oKQtsP64nmoLdUeFG2jJHNaBf37wdcEpEjljBc8oi3EnJ7x--Pf5th-lJPTtNJZ_8cHbcBaUzuyS2_sTVjAaguWvZrk-xas3DV98m14utFjF8MoL7Hryo48EyvruSMsFpkLAk5OqWaabo4m7sQQLdz_msWqGRWz7AHJ0ZHdeiGTD70Dj53r_tVN0CgoBCZOxCQoU4Gm4DKJhYwoKqObQdaU4bVSlhdkp0yWMXJVWrJXYYvIytSGGOmScxuj2IVWNapwHxiWKixSa0NuRWyNKAwXClGrLJUm1qINZwRs_uI5MnLf2xa5xypvsGrD6Qz3nNzY9SZ0hQRAzpVT0XJb4zbseYPM1xJZmDpi-oO_vOIQVjnVHe63b5QeQWsyfsVjWDJvk2E9PoFFOcjo2u3dnUw96BNsjcRg |
| linkProvider | Oxford University Press |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Harnessing+Endogenous+Peptide+Compounds+as+Potential+Therapeutics+for+Severe+Influenza&rft.jtitle=The+Journal+of+infectious+diseases&rft.au=West%2C+Alison+C&rft.au=Harpur%2C+Christopher+M&rft.au=Le+Page%2C+M%C3%A9lanie+A&rft.au=Lam%2C+Maggie&rft.date=2024-08-16&rft.pub=Oxford+University+Press&rft.issn=0022-1899&rft.eissn=1537-6613&rft.volume=230&rft.issue=2&rft.spage=e384&rft.epage=e394&rft_id=info:doi/10.1093%2Finfdis%2Fjiad566&rft.externalDocID=10.1093%2Finfdis%2Fjiad566 |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=0022-1899&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=0022-1899&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=0022-1899&client=summon |