Recombinant superoxide dismutase (SOD) administered by aerosol inhibits respiratory syncytial virus infection in cotton rats

Wyde, Philip R.; Moore, Donna K.; Pimentel, D.Miles; Gilbert, Brian E.; Nimrod, Rami; Panet, Amos

doi:10.1016/0166-3542(95)06967-4

Cited by 21 publications

(11 citation statements)

References 21 publications

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“…Despite the high activity, selectivity and virusspecificity of these and other peptides and proteins [68][69][70][71][72] against RSV infection, it is difficult to use them because of their "undesirable pharmaceutical and biopharmaceutical properties". Therefore, numerous prodrug systems are being developed to improve the stability, water solubility and they have not been tested against RSV in vivo and the mechanism of action for all substances mentioned below was not reported.…”

Section: Inhibitors Of Fusionmentioning

confidence: 99%

Novel Anti-RSV Dianionic Dendrimer-Like Compounds: Design, Synthesis and Biological Evaluation

Gazumyan¹,

Mitsner²,

Ellestad³

2000

CPD

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Human Respiratory Syncytial Virus (RSV) is considered to be the leading cause of lower respiratory tract disease in infants and young children. RSV is also a common pathogen in immunocompromised adults and in the elderly. RSV infection can be epidemic and is evident worldwide. Ribavirin, a small molecule agent, and Synagis, a monoclonal neutralizing antibody, are the only approved drugs for treatment and prevention of RSV in high-risk patients. This review is focused on a group of novel and specific inhibitors discovered at Wyeth-Ayerst Research. Some of these inhibitors have IC50 <50 nM and are active against all the tested group A and B viruses. They also have shown good efficacy in cotton rats and primates. Mechanism of action studies indicate that the compounds inhibit the next step in infection after adsorption suggesting that fusion is the target. A strong relationship between the inhibitor structures and their anti-RSV activity was established. This relationship appears to derive from a multivalent interaction between the functional groupings of the inhibitors and the F protein, which seem to be highly complementary and directional.

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Section: Inhibitors Of Fusionmentioning

confidence: 99%

Novel Anti-RSV Dianionic Dendrimer-Like Compounds: Design, Synthesis and Biological Evaluation

Gazumyan¹,

Mitsner²,

Ellestad³

2000

CPD

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“…Treatment with NAC reduces viral burden in vivo (188). The administration of aerosols containing SOD reduced the pulmonary RSV load in rats (348), whereas synthetic catalytic scavengers that possess SOD, catalase, and glutathione-peroxidase activity reduced viral replication in human epithelial pulmonary cell (115). Similarly, Nrf2 -/mice present increased RSV replication compared with wild-type mice, which can be verified as soon as 1 day after infection (49).…”

mentioning

confidence: 93%

Are Reactive Oxygen Species Always Detrimental to Pathogens?

Paiva

Bozza²

2014

Antioxidants & Redox Signaling

434

345

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Reactive oxygen species (ROS) are deadly weapons used by phagocytes and other cell types, such as lung epithelial cells, against pathogens. ROS can kill pathogens directly by causing oxidative damage to biocompounds or indirectly by stimulating pathogen elimination by various nonoxidative mechanisms, including pattern recognition receptors signaling, autophagy, neutrophil extracellular trap formation, and T-lymphocyte responses. Thus, one should expect that the inhibition of ROS production promote infection. Increasing evidences support that in certain particular infections, antioxidants decrease and prooxidants increase pathogen burden. In this study, we review the classic infections that are controlled by ROS and the cases in which ROS appear as promoters of infection, challenging the paradigm. We discuss the possible mechanisms by which ROS could promote particular infections. These mechanisms are still not completely clear but include the metabolic effects of ROS on pathogen physiology, ROS-induced damage to the immune system, and ROS-induced activation of immune defense mechanisms that are subsequently hijacked by particular pathogens to act against more effective microbicidal mechanisms of the immune system. The effective use of antioxidants as therapeutic agents against certain infections is a realistic possibility that is beginning to be applied against viruses.

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“…Small-molecule hRSV-specific fusion inhibitors have neutralizing activity against A and B group hRSV isolates in vitro and in vivo via blockade of cell-cell fusion (179,258,272), while a benzodithiin compound has demonstrated ability to interfere with intracellular processing of the hRSV fusion protein, thereby resulting in decreased infectivity (333). Other agents reported to have anti-hRSV activity have included crude plant protein extracts (3), some forms of superoxide dismutase (384), an L-aspartate transcarbamoylase inhibitor (383), eosinophil-derived neurotoxin, a potent RNase (87), and lovastatin (144).…”

Section: Therapy For Hrsv Diseasementioning

confidence: 99%

Animal Pneumoviruses: Molecular Genetics and Pathogenesis

2004

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Pneumoviruses are single-stranded, negative-sense, nonsegmented RNA viruses of the family Paramyxoviridae, subfamily Pneumovirinae, and include pathogens that infect humans (respiratory syncytial virus and human metapneumovirus), domestic mammals (bovine, ovine, and caprine respiratory syncytial viruses), rodents (pneumonia virus of mice), and birds (avian metapneumovirus). Among the topics considered in this review are recent studies focused on the roles of the individual virus-encoded components in promoting virus replication as well as in altering and evading innate antiviral host defenses. Advances in the molecular technology of pneumoviruses and the emergence of recombinant pneumoviruses that are leading to improved virus-based vaccine formulations are also discussed. Since pneumovirus infection in natural hosts is associated with a profound inflammatory response that persists despite adequate antiviral therapy, we also review the recent experimental treatment strategies that have focused on combined antiviral, anti-inflammatory, and immunomodulatory approaches

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Recombinant superoxide dismutase (SOD) administered by aerosol inhibits respiratory syncytial virus infection in cotton rats

Cited by 21 publications

References 21 publications

Novel Anti-RSV Dianionic Dendrimer-Like Compounds: Design, Synthesis and Biological Evaluation

Novel Anti-RSV Dianionic Dendrimer-Like Compounds: Design, Synthesis and Biological Evaluation

Are Reactive Oxygen Species Always Detrimental to Pathogens?

Animal Pneumoviruses: Molecular Genetics and Pathogenesis

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