Identification of Anti-Influenza A Compounds Inhibiting the Viral Non-Structural Protein 1 (NS1) Using a Type I Interferon-Driven Screening Strategy
There is an urgent need to identify efficient antiviral compounds to combat existing and emerging RNA virus infections, particularly those related to seasonal and pandemic influenza outbreaks. While inhibitors of the influenza viral integral membrane proton channel protein (M2), neuraminidase (NA), and cap-dependent endonuclease are available, circulating influenza viruses acquire resistance over time. Thus, the need for the development of additional anti-influenza drugs with novel mechanisms of action exists. In the present study, a cell-based screening assay and a small molecule library were used to screen for activities that antagonized influenza A non-structural protein 1 (NS1), a highly conserved, multifunctional accessory protein that inhibits the type I interferon response against influenza. Two potential anti-influenza agents, compounds 157 and 164, were identified with anti-NS1 activity, resulting in the reduction of A/PR/8/34(H1N1) influenza A virus replication and the restoration of IFN-β expression in human lung epithelial A549 cells. A 3D pharmacophore modeling study of the active compounds provided a glimpse of the structural motifs that may contribute to anti-influenza virus activity. This screening approach is amenable to a broader analysis of small molecule compounds to inhibit other viral targets.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:24 |
|---|---|
| Enthalten in: |
International journal of molecular sciences - 24(2023), 13 vom: 22. Juni |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Marsili, Giulia [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 17.07.2023 Date Revised 18.07.2023 published: Electronic Citation Status MEDLINE |
|---|
| doi: |
10.3390/ijms241310495 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM359464173 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM359464173 | ||
| 003 | DE-627 | ||
| 005 | 20231226080930.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.3390/ijms241310495 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1198.xml |
| 035 | |a (DE-627)NLM359464173 | ||
| 035 | |a (NLM)37445672 | ||
| 035 | |a (PII)10495 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Marsili, Giulia |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Identification of Anti-Influenza A Compounds Inhibiting the Viral Non-Structural Protein 1 (NS1) Using a Type I Interferon-Driven Screening Strategy |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 17.07.2023 | ||
| 500 | |a Date Revised 18.07.2023 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a There is an urgent need to identify efficient antiviral compounds to combat existing and emerging RNA virus infections, particularly those related to seasonal and pandemic influenza outbreaks. While inhibitors of the influenza viral integral membrane proton channel protein (M2), neuraminidase (NA), and cap-dependent endonuclease are available, circulating influenza viruses acquire resistance over time. Thus, the need for the development of additional anti-influenza drugs with novel mechanisms of action exists. In the present study, a cell-based screening assay and a small molecule library were used to screen for activities that antagonized influenza A non-structural protein 1 (NS1), a highly conserved, multifunctional accessory protein that inhibits the type I interferon response against influenza. Two potential anti-influenza agents, compounds 157 and 164, were identified with anti-NS1 activity, resulting in the reduction of A/PR/8/34(H1N1) influenza A virus replication and the restoration of IFN-β expression in human lung epithelial A549 cells. A 3D pharmacophore modeling study of the active compounds provided a glimpse of the structural motifs that may contribute to anti-influenza virus activity. This screening approach is amenable to a broader analysis of small molecule compounds to inhibit other viral targets | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a NS1 | |
| 650 | 4 | |a diverse compound library | |
| 650 | 4 | |a influenza A viruses | |
| 650 | 4 | |a luciferase reporter assay | |
| 650 | 4 | |a pharmacophore modeling | |
| 650 | 4 | |a small molecule screening | |
| 650 | 4 | |a type I IFN | |
| 650 | 7 | |a Interferon Type I |2 NLM | |
| 650 | 7 | |a Viral Nonstructural Proteins |2 NLM | |
| 650 | 7 | |a Antiviral Agents |2 NLM | |
| 700 | 1 | |a Acchioni, Chiara |e verfasserin |4 aut | |
| 700 | 1 | |a Remoli, Anna Lisa |e verfasserin |4 aut | |
| 700 | 1 | |a Amatore, Donatella |e verfasserin |4 aut | |
| 700 | 1 | |a Sgarbanti, Rossella |e verfasserin |4 aut | |
| 700 | 1 | |a De Angelis, Marta |e verfasserin |4 aut | |
| 700 | 1 | |a Orsatti, Roberto |e verfasserin |4 aut | |
| 700 | 1 | |a Acchioni, Marta |e verfasserin |4 aut | |
| 700 | 1 | |a Astolfi, Andrea |e verfasserin |4 aut | |
| 700 | 1 | |a Iraci, Nunzio |e verfasserin |4 aut | |
| 700 | 1 | |a Puzelli, Simona |e verfasserin |4 aut | |
| 700 | 1 | |a Facchini, Marzia |e verfasserin |4 aut | |
| 700 | 1 | |a Perrotti, Edvige |e verfasserin |4 aut | |
| 700 | 1 | |a Cecchetti, Violetta |e verfasserin |4 aut | |
| 700 | 1 | |a Sabatini, Stefano |e verfasserin |4 aut | |
| 700 | 1 | |a Superti, Fabiana |e verfasserin |4 aut | |
| 700 | 1 | |a Agamennone, Mariangela |e verfasserin |4 aut | |
| 700 | 1 | |a Barreca, Maria Letizia |e verfasserin |4 aut | |
| 700 | 1 | |a Hiscott, John |e verfasserin |4 aut | |
| 700 | 1 | |a Nencioni, Lucia |e verfasserin |4 aut | |
| 700 | 1 | |a Sgarbanti, Marco |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t International journal of molecular sciences |d 2008 |g 24(2023), 13 vom: 22. Juni |w (DE-627)NLM185552161 |x 1422-0067 |7 nnns |
| 773 | 1 | 8 | |g volume:24 |g year:2023 |g number:13 |g day:22 |g month:06 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.3390/ijms241310495 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 24 |j 2023 |e 13 |b 22 |c 06 | ||