AMG487 inhibits PRRSV replication and ameliorates lung injury in pig lung xenografts by down-regulating the expression of ANXA2

Liu, Jie; Yao, Lun; Huang, Shuguang; Wang, Binyu; Li, Linrui; Li, Lexing; Gu, Wei; Xiao, Shaobo; Liu, Guoquan

doi:10.1016/j.antiviral.2022.105314

Cited by 6 publications

(7 citation statements)

References 54 publications

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“…In the present study, AMG487 but not anti-IFN-γ decreased the (Liu et al, 2022;Ojha et al, 2019). AMG487 can also reduce H5N1 influenza viral load in the lung of ferrets (Cameron et al, 2008).…”

Section: Discussioncontrasting

confidence: 41%

“…AMG487 significantly improves the survival of mice from Japanese encephalitis virus infection through inhibiting viral replication (Ojha et al, 2019). AMG487 also ameliorates lung injury induced by Porcine reproductive and respiratory syndrome virus in pig lung xenografts through suppressing viral replication (Liu et al, 2022). AMG487 results in a reduction of symptom severity and delayed mortality in H5N1 influenza virus-infected ferrets through reducing pulmonary viral loads (Cameron et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

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AMG487 alleviates influenza A (H1N1) virus‐induced pulmonary inflammation through decreasing IFN‐γ‐producing lymphocytes and IFN‐γ concentrations

Ding,

Li,

Song

et al. 2024

British J Pharmacology

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Background and PurposeSevere influenza virus‐infected patients have high systemic levels of Th1 cytokines (including IFN‐γ). Intrapulmonary IFN‐γ increases pulmonary IFN‐γ‐producing T lymphocytes through the CXCR3 pathway. Virus‐infected mice lacking IP‐10/CXCR3 demonstrate lower pulmonary neutrophilic inflammation. AMG487, an IP‐10/CXCR3 antagonist, ameliorates virus‐induced lung injury in vivo through decreasing viral loads. This study examined whether AMG487 could treat H1N1 virus‐induced mouse illness through reducing viral loads or decreasing the number of lymphocytes or neutrophils.Experimental ApproachHere, we studied the above‐mentioned effects and underlying mechanisms in vivo.Key ResultsH1N1 virus infection caused bad overall condition and pulmonary inflammation characterized by the infiltration of lymphocytes and neutrophils. From Day‐5 to Day‐10 post‐virus infection, bad overall condition, pulmonary lymphocytes, and IFN‐γ concentrations increased, while pulmonary H1N1 viral titres and neutrophils decreased. Both anti‐IFN‐γ and AMG487 alleviated virus infection‐induced bad overall condition and pulmonary lymphocytic inflammation. Pulmonary neutrophilic inflammation was mitigated by AMG487 on Day‐5 post‐infection, but was not mitigated by AMG487 on Day‐10 post‐infection. H1N1 virus induced increases of IFN‐γ, IP‐10, and IFN‐γ‐producing lymphocytes and activation of the Jak2‐Stat1 pathways in mouse lungs, which were inhibited by AMG487. Anti‐IFN‐γ decreased IFN‐γ and IFN‐γ‐producing lymphocytes on Day‐5 post‐infection. AMG487 but not anti‐IFN‐γ decreased viral titres in mouse lung homogenates or BALF. Higher virus load did not increase pulmonary inflammation and IFN‐γ concentrations when mice were treated with AMG487.Conclusion and ImplicationsAMG487 may ameliorate H1N1 virus‐induced pulmonary inflammation through decreasing IFN‐γ‐producing lymphocytes rather than reducing viral loads or neutrophils.

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Section: Discussioncontrasting

confidence: 41%

Section: Introductionmentioning

confidence: 99%

AMG487 alleviates influenza A (H1N1) virus‐induced pulmonary inflammation through decreasing IFN‐γ‐producing lymphocytes and IFN‐γ concentrations

Ding,

Li,

Song

et al. 2024

British J Pharmacology

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“…Interestingly, the knockout of Annexin A2 significantly reduced the viral and RNA copy numbers of progeny, indicating the importance of Annexin A2 in PRRSV infection [ 73 ]. Furthermore, Liu et al [ 74 ] established a pig lung transplantation model of PRRSV infection in immunodeficient mice and successfully used this model to verify that the CXCR3 antagonist AMG487 effectively inhibited PRRSV infection and alleviated lung injury by down-regulating the expression of Annexin A2. It is worth considering whether CXCR3 antagonists can be used in the treatment of patients with COVID-19 to decrease the concentration of Annexin A2.…”

Section: Nidovirusmentioning

confidence: 99%

Annexin A2: the missing piece in the puzzle of pathogen-induced damage

Liao

et al. 2023

Virulence

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Annexin A2 is a Ca 2+ regulated protein belonging to the Annexin family and is found in the cytoplasm and cell membrane. It can exist in a monomeric form or in a heterotetrameric form with the S100A10 dimer. The research on Annexin A2 in tumours is currently active, and studies on its role in pathogen infection are increasing. Annexin A2 plays a crucial role in the life cycle of viruses by mediating adhesion, internalization, uncoating, transport, and release. In the case of parasites, bacteria, mycoplasma, fungi, and other pathogens, Annexin A2 binds to the ligand on the pathogen, which mediates the pathogen’s adhesion to the host cell, ultimately leading to infection and damage to the host. Furthermore, some studies have developed biological or chemical drugs that target Annexin A2, which have demonstrated promising anti-infective effects. Thus, targeting Annexin A2 may present a promising therapeutic approach for the treatment of diverse infectious diseases. In summary, this paper provides an overview of Annexin A2 and its role in various pathogens. It highlights its regulation of pathogen infection and its potential as a therapeutic target for the treatment of infectious diseases.

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“…Porcine reproductive and respiratory syndrome (PRRS) is the most economically impactful viral disease affecting swine globally, known for causing severe reproductive disorders in pregnant sows and respiratory illnesses in pigs of all age groups. 1 The PRRS is caused by the PRRS virus (PRRSV), an enveloped single-stranded positive RNA virus that falls under the genus Porartevirus, family Arteriviridae, and order Nidovirales. 2 This viral disease was initially documented in the United States during the late 1980s and swiftly expanded across the globe.…”

Section: ■ Introductionmentioning

confidence: 99%

Zinc Oxide–Selenium Nanoparticles for Inhibiting the Proliferation of Porcine Reproductive and Respiratory Syndrome Virus

Xu,

Li,

Chen

et al. 2024

ACS Appl. Nano Mater.

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Porcine Reproductive and Respiratory Syndrome (PRRS) is an acute, highly contagious swine infectious disease caused by the PRRS virus (PRRSV). Due to the frequent mutation and recombination of PRRSV, the current commercial vaccines cannot provide effective protection, and there is an urgent need to develop antiviral drugs. This study aimed to prepare a kind of zinc oxide−selenium nanoparticle (ZnO−Se NPs) and investigate their inhibitory effect on PRRSV proliferation. The hybridization of ZnO and selenium resulted in the synthesis of ZnO−Se NPs, which were then examined by using dynamic laser light scattering and transmission electron microscopy for characterization. The ZnO−Se NPs showed excellent stability and dispersibility, measuring an average diameter of 90 nm. MTT assay revealed that ZnO−Se NPs had good biocompatibility and low toxicity below 2.5 μg/mL. Various experiments have shown that ZnO−Se NPs have the ability to effectively suppress the proliferation of PRRSV in a dose-dependent fashion. Moreover, this inhibition was equally effective against other subgenotypes of PRRSV and non-RNA viruses, indicating that ZnO−Se NPs had broad-spectrum antimicrobial properties. Mechanism investigations revealed that ZnO−Se NPs inhibited PRRSV primarily by targeting the replication process through upregulation of the expression of NLRX1, a protein that interacts with PRRSV Nsp9, and by inhibiting PRRSV-induced upregulation of ROS, rather than by stimulating the innate immunity. This work emphasized the antiviral impact of ZnO−Se NPs and offered compelling evidence of their potential as a promising therapy against PRRSV and other viral infections.

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AMG487 inhibits PRRSV replication and ameliorates lung injury in pig lung xenografts by down-regulating the expression of ANXA2

Cited by 6 publications

References 54 publications

AMG487 alleviates influenza A (H1N1) virus‐induced pulmonary inflammation through decreasing IFN‐γ‐producing lymphocytes and IFN‐γ concentrations

AMG487 alleviates influenza A (H1N1) virus‐induced pulmonary inflammation through decreasing IFN‐γ‐producing lymphocytes and IFN‐γ concentrations

Annexin A2: the missing piece in the puzzle of pathogen-induced damage

Zinc Oxide–Selenium Nanoparticles for Inhibiting the Proliferation of Porcine Reproductive and Respiratory Syndrome Virus

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