Aloperine Inhibits ASFV via Regulating PRLR/JAK2 Signaling Pathway In Vitro
African swine fever (ASF) has become a global pandemic due to inadequate prevention and control measures, posing a significant threat to the swine industry. Despite the approval of a single vaccine in Vietnam, no antiviral drugs against the ASF virus (ASFV) are currently available. Aloperine (ALO),...
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| Veröffentlicht in: | International journal of molecular sciences 2024-08, Vol.25 (16), p.9083 |
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| creator | Geng, Renhao Shao, Hongxia Qian, Kun Chen, Hongjun Qin, Aijian |
| description | African swine fever (ASF) has become a global pandemic due to inadequate prevention and control measures, posing a significant threat to the swine industry. Despite the approval of a single vaccine in Vietnam, no antiviral drugs against the ASF virus (ASFV) are currently available. Aloperine (ALO), a quinolizidine alkaloid extracted from the seeds and leaves of bitter beans, exhibits various biological functions, including anti-inflammatory, anti-cancer, and antiviral activities. In this study, we found that ALO could inhibit ASFV replication in MA-104, PK-15, 3D4/21, and WSL cells in a dose-dependent manner without cytotoxicity at 100 μM. Furthermore, it was verified that ALO acted on the co- and post-infection stages of ASFV by time-of-addition assay, and inhibited viral internalization rather than directly inactivating the virus. Notably, RT-qPCR analysis indicated that ALO did not exert anti-inflammatory activity during ASFV infection. Additionally, gene ontology (GO) and KEGG pathway enrichment analyses of transcriptomic data revealed that ALO could inhibit ASFV replication via the PRLR/JAK2 signaling pathway. Together, these findings suggest that ALO effectively inhibits ASFV replication in vitro and provides a potential new target for developing anti-ASFV drugs. |
| doi_str_mv | 10.3390/ijms25169083 |
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Despite the approval of a single vaccine in Vietnam, no antiviral drugs against the ASF virus (ASFV) are currently available. Aloperine (ALO), a quinolizidine alkaloid extracted from the seeds and leaves of bitter beans, exhibits various biological functions, including anti-inflammatory, anti-cancer, and antiviral activities. In this study, we found that ALO could inhibit ASFV replication in MA-104, PK-15, 3D4/21, and WSL cells in a dose-dependent manner without cytotoxicity at 100 μM. Furthermore, it was verified that ALO acted on the co- and post-infection stages of ASFV by time-of-addition assay, and inhibited viral internalization rather than directly inactivating the virus. Notably, RT-qPCR analysis indicated that ALO did not exert anti-inflammatory activity during ASFV infection. Additionally, gene ontology (GO) and KEGG pathway enrichment analyses of transcriptomic data revealed that ALO could inhibit ASFV replication via the PRLR/JAK2 signaling pathway. Together, these findings suggest that ALO effectively inhibits ASFV replication in vitro and provides a potential new target for developing anti-ASFV drugs.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms25169083</identifier><identifier>PMID: 39201769</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>African Swine Fever - metabolism ; African Swine Fever - virology ; African Swine Fever Virus - drug effects ; African Swine Fever Virus - metabolism ; Animals ; Antiviral Agents - pharmacology ; Cell cycle ; Cell Line ; Cytokines ; Cytotoxicity ; Genes ; Hepatitis ; Hogs ; Infections ; Janus Kinase 2 - metabolism ; Mortality ; Piperidines - pharmacology ; Protein expression ; Proteins ; Quinolizidines - pharmacology ; Signal transduction ; Signal Transduction - drug effects ; Swine ; Vaccines ; Virus Replication - drug effects ; Viruses</subject><ispartof>International journal of molecular sciences, 2024-08, Vol.25 (16), p.9083</ispartof><rights>2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). 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Despite the approval of a single vaccine in Vietnam, no antiviral drugs against the ASF virus (ASFV) are currently available. Aloperine (ALO), a quinolizidine alkaloid extracted from the seeds and leaves of bitter beans, exhibits various biological functions, including anti-inflammatory, anti-cancer, and antiviral activities. In this study, we found that ALO could inhibit ASFV replication in MA-104, PK-15, 3D4/21, and WSL cells in a dose-dependent manner without cytotoxicity at 100 μM. Furthermore, it was verified that ALO acted on the co- and post-infection stages of ASFV by time-of-addition assay, and inhibited viral internalization rather than directly inactivating the virus. Notably, RT-qPCR analysis indicated that ALO did not exert anti-inflammatory activity during ASFV infection. Additionally, gene ontology (GO) and KEGG pathway enrichment analyses of transcriptomic data revealed that ALO could inhibit ASFV replication via the PRLR/JAK2 signaling pathway. 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Despite the approval of a single vaccine in Vietnam, no antiviral drugs against the ASF virus (ASFV) are currently available. Aloperine (ALO), a quinolizidine alkaloid extracted from the seeds and leaves of bitter beans, exhibits various biological functions, including anti-inflammatory, anti-cancer, and antiviral activities. In this study, we found that ALO could inhibit ASFV replication in MA-104, PK-15, 3D4/21, and WSL cells in a dose-dependent manner without cytotoxicity at 100 μM. Furthermore, it was verified that ALO acted on the co- and post-infection stages of ASFV by time-of-addition assay, and inhibited viral internalization rather than directly inactivating the virus. Notably, RT-qPCR analysis indicated that ALO did not exert anti-inflammatory activity during ASFV infection. Additionally, gene ontology (GO) and KEGG pathway enrichment analyses of transcriptomic data revealed that ALO could inhibit ASFV replication via the PRLR/JAK2 signaling pathway. Together, these findings suggest that ALO effectively inhibits ASFV replication in vitro and provides a potential new target for developing anti-ASFV drugs.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>39201769</pmid><doi>10.3390/ijms25169083</doi><orcidid>https://orcid.org/0000-0002-7254-7596</orcidid><orcidid>https://orcid.org/0000-0002-8900-1848</orcidid><orcidid>https://orcid.org/0000-0001-5779-273X</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | African Swine Fever - metabolism African Swine Fever - virology African Swine Fever Virus - drug effects African Swine Fever Virus - metabolism Animals Antiviral Agents - pharmacology Cell cycle Cell Line Cytokines Cytotoxicity Genes Hepatitis Hogs Infections Janus Kinase 2 - metabolism Mortality Piperidines - pharmacology Protein expression Proteins Quinolizidines - pharmacology Signal transduction Signal Transduction - drug effects Swine Vaccines Virus Replication - drug effects Viruses |
| title | Aloperine Inhibits ASFV via Regulating PRLR/JAK2 Signaling Pathway In Vitro |
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