Anthrax Lethal Factor Inhibitors as Potential Countermeasure of the Infection

Kumar, B.V.S. Suneel; Malik, Siddharth; Grandhi, Pradeep; Dayam, Raveendra; Sarma, J. A. R. P.

doi:10.2174/1568026614666140929120231

Cited by 6 publications

(11 citation statements)

References 40 publications

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“…Inhalational anthrax presents itself as a respiratory infection, resulting in death ~48 days from symptom onset. 604 Left untreated, inhalational anthrax has mortality rates of 100%, and even when treated with antibiotics the mortality rate is 70%. 603…”

Section: Peptidases (Ec 34)mentioning

confidence: 99%

“…The release of the anthrax LF crystal structure in 2001 610 spurred inhibitor development against this target. 604 By far the most studied class of inhibitor against LF utilizes the hydroxamic acid MBP (Figure 67, Table 9). This class of inhibitor coordinates to the Zn 2+ ion through the hydroxamate MBP in the typical bidentate manner, which effectively blocks the active site.…”

Section: Peptidases (Ec 34)mentioning

confidence: 99%

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Targeting Metalloenzymes for Therapeutic Intervention

et al. 2018

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Metalloenzymes are central to a wide range of essential biological activities, including nucleic acid modification, protein degradation, and many others. The role of metalloenzymes in these processes also makes them central for the progression of many diseases and, as such, makes metalloenzymes attractive targets for therapeutic intervention. Increasing awareness of the role metalloenzymes play in disease and their importance as a class of targets has amplified interest in the development of new strategies to develop inhibitors and ultimately useful drugs. In this Review, we provide a broad overview of several drug discovery efforts focused on metalloenzymes and attempt to map out the current landscape of high-value metalloenzyme targets.

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Section: Peptidases (Ec 34)mentioning

confidence: 99%

Section: Peptidases (Ec 34)mentioning

confidence: 99%

Targeting Metalloenzymes for Therapeutic Intervention

et al. 2018

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“…anthracis is a causative agent of anthrax disease, which is a zoonosis manifested in various forms. Cutaneous form starts, when spores or cells penetrate skin; gastrointestinal form follows ingestion of cells or spores and pulmonary form is the last and the most lethal type of anthrax following inhalation of spores or cells (21,22). Each of the anthrax forms can lead to a very serious meningitis and bacteremia (23).…”

Section: Bacillus Anthracis: a Causative Agent Of Anthraxmentioning

confidence: 99%

Bacillus anthracis as a biological warfare agent: infection, diagnosis and countermeasures

Pohanka¹

2020

BLL

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Bacillus anthracis is a causative agent of zoonotic anthrax disease. In the last years, signifi cant progress in therapy and diagnosis of anthrax was made. Concurrently, knowledge about anthrax progression, molecular pathology and release of anthrax toxin during the disease has improved. This review covers the recent progress in this fi eld. METHODS: In this review, specifi cations of B. anthracis, anthrax disease, medical and biomedical countermeasures and diagnostic tools were surveyed. The actual literature was summarized and relevance of the microorganism as a biological warfare agent and the ways how to reduce its impact including therapeutic protocols were written and discussed. RESULTS: Currently, the microorganism is considered one of the top biological warfare agents due to lethality, long term stability of spores, easy dissemination and production. The recent research is focused on countermeasures suitable for reduction of consequences by a misuse of the microorganism in form of biological weapon (Tab.

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“…Once in the cytosol, LF and EF exert their individual effects. Categorization of potential toxin-directed agents for anthrax can be done in the context of the steps required for toxin uptake by cells [26,27,30,34]. …”

Section: Toxin Uptake During Infectionmentioning

confidence: 99%

An overview of investigational toxin-directed therapies for the adjunctive management ofBacillus anthracisinfection and sepsis

Ohanjanian

Remy

et al. 2015

Expert Opinion on Investigational Drugs

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Introduction Sepsis with Bacillus anthracis infection has a very high mortality rate despite appropriate antibiotic and supportive therapies. Over the past 15 years, recent outbreaks in the US and in Europe, coupled with anthrax's bioterrorism weapon potential, have stimulated efforts to develop adjunctive therapies to improve clinical outcomes. Since lethal toxin and edema toxin (LT and ET) make central contributions to the pathogenesis of B. anthracis, these have been major targets in this effort. Areas covered Here, the authors review different investigative biopharmaceuticals that have been recently identified for their therapeutic potential as inhibitors of LT or ET. Among these inhibitors are two antibody preparations that have been included in the Strategic National Stockpile (SNS) and several more that have reached Phase I testing. Presently, however, many of these candidate agents have only been studied in vitro and very few tested in bacteria-challenged models. Expert opinion Although a large number of drugs have been identified as potential therapeutic inhibitors of LT and ET, in most cases their testing has been limited. The use of the two SNS antibody therapies during a large-scale exposure to B. anthracis will be difficult. Further testing and development of agents with oral bioavailability and relatively long shelf lives should be a focus for future research.

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Anthrax Lethal Factor Inhibitors as Potential Countermeasure of the Infection

Cited by 6 publications

References 40 publications

Targeting Metalloenzymes for Therapeutic Intervention

Targeting Metalloenzymes for Therapeutic Intervention

Bacillus anthracis as a biological warfare agent: infection, diagnosis and countermeasures

An overview of investigational toxin-directed therapies for the adjunctive management ofBacillus anthracisinfection and sepsis

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