SARS-CoV-2-derived fusion inhibitor lipopeptides exhibit highly potent and broad-spectrum activity against divergent human coronaviruses

ABSTRACTThis study summarizes the topical E-101 solution susceptibility testing results for 760 Gram-positive and Gram-negative target pathogens collected from 75 U.S. sites between 2008 and 2012 and 103 ESKAPE pathogens. E-101 solution maintained potent activity against all bacterial species studied for each year tested, with MICs ranging from <0.008 to 0.25 μg porcine myeloperoxidase (pMPO)/ml. These results confirm that E-101 solution retains its potent broad-spectrum activity against U.S. clinical isolates and organisms with challenging resistance phenotypes.

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Efficacy of some medicated soaps and hand washes available in market

International Journal of Science and Research Archive ◽

10.30574/ijsra.2021.3.1.0098 ◽

2021 ◽

Vol 3 (1) ◽

pp. 047-055

Author(s):

Pimpliskar Mukesh ◽

SoumyaGounder ◽

Rahul Jadhav

Keyword(s):

Broad Spectrum ◽

Life Forms ◽

Small Scale ◽

Gram Positive ◽

Consistent Finding ◽

Gram Negative ◽

Cross Transmission ◽

Spectrum Activity ◽

Significant Measure ◽

Broad Spectrum Activity

Background: Handwashing is underlined as the absolute most significant measure to forestall cross-transmission of small-scale life forms and consequently to forestall nosocomial contaminations. Be that as it may, under routine emergency clinic practice consistent with this measure is still unsatisfactorily low, under half in many investigations distributed in the previous 20 years. This consistent finding is stressing because ongoing investigations have demonstrated that this degree of consistency won't decrease the danger of transmission of multi- medicate safe microscopic organisms in the emergency clinics. Results: In the present investigation effect of marketed hand washed namely Lifebuoy, Dettol and Savlon were tested on bacteria E. coli, S.aureus, S.pyogen, Klebshiella and, fungi Candida albicans. All the handwash at concentrated level found to be effective but only Dettol hand wash could give inhibitory action at 25ug/ml against Klebshiella while others at50ug/ml. Conclusions: Soapex and Dettol soap had broad spectrum activity as it inhibited the growth of Gram positive (Streptococcus pyogen) and Gram-negative (Escherichia coli). Liquid handwash such as Lifebuoy,Dettol and Savlon showed broad spectrum activity on both Gram-positive and Gram negative test microorganisms.

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Correction: Novel broad-spectrum activity-based probes to profile malarial cysteine proteases

PLoS ONE ◽

10.1371/journal.pone.0231231 ◽

2020 ◽

Vol 15 (3) ◽

pp. e0231231

Author(s):

Michele S. Y. Tan ◽

Dara Davison ◽

Mateo I. Sanchez ◽

Bethany M. Anderson ◽

Stephen Howell ◽

...

Keyword(s):

Broad Spectrum ◽

Cysteine Proteases ◽

Spectrum Activity ◽

Broad Spectrum Activity

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Rational design, synthesis and testing of novel tricyclic topoisomerase inhibitors for the treatment of bacterial infections part 2

RSC Medicinal Chemistry ◽

10.1039/d0md00175a ◽

2020 ◽

Vol 11 (12) ◽

pp. 1379-1385

Author(s):

R. Kirk ◽

A. Ratcliffe ◽

G. Noonan ◽

M. Uosis-Martin ◽

D. Lyth ◽

...

Keyword(s):

Broad Spectrum ◽

Bacterial Infections ◽

Rational Design ◽

Topoisomerase Ii ◽

Topoisomerase Inhibitors ◽

Design Synthesis ◽

Pharmacokinetic Properties ◽

Spectrum Activity ◽

Broad Spectrum Activity

We disclose the discovery of REDX07965, a novel tricyclic topoisomerase inhibitor (NTTI) which has broad spectrum activity, favourable in vitro pharmacokinetic properties and selectivity versus human topoisomerase II.

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Alkoxyphenylthiazoles with broad-spectrum activity against multidrug-resistant gram-positive bacterial pathogens

European Journal of Medicinal Chemistry ◽

10.1016/j.ejmech.2018.04.049 ◽

2018 ◽

Vol 152 ◽

pp. 318-328 ◽

Cited By ~ 14

Author(s):

Moustafa ElAwamy ◽

Haroon Mohammad ◽

Abdelrahman Hussien ◽

Nader S. Abutaleb ◽

Mohamed Hagras ◽

...

Keyword(s):

Broad Spectrum ◽

Bacterial Pathogens ◽

Multidrug Resistant ◽

Gram Positive ◽

Spectrum Activity ◽

Broad Spectrum Activity

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Identification of Broad-Spectrum Antiviral Compounds by Targeting Viral Entry

Viruses ◽

10.3390/v11020176 ◽

2019 ◽

Vol 11 (2) ◽

pp. 176 ◽

Cited By ~ 20

Author(s):

Michela Mazzon ◽

Ana Ortega-Prieto ◽

Douglas Imrie ◽

Christin Luft ◽

Lena Hess ◽

...

Keyword(s):

Viral Entry ◽

Broad Spectrum ◽

Well Being ◽

Screening Strategy ◽

Life Cycles ◽

Antiviral Compounds ◽

Spectrum Activity ◽

Cellular Pathways ◽

Broad Spectrum Activity ◽

Economic Well Being

Viruses are a major threat to human health and economic well-being. In recent years Ebola, Zika, influenza, and chikungunya virus epidemics have raised awareness that infections can spread rapidly before vaccines or specific antagonists can be made available. Broad-spectrum antivirals are drugs with the potential to inhibit infection by viruses from different groups or families, which may be deployed during outbreaks when specific diagnostics, vaccines or directly acting antivirals are not available. While pathogen-directed approaches are generally effective against a few closely related viruses, targeting cellular pathways used by multiple viral agents can have broad-spectrum efficacy. Virus entry, particularly clathrin-mediated endocytosis, constitutes an attractive target as it is used by many viruses. Using a phenotypic screening strategy where the inhibitory activity of small molecules was sequentially tested against different viruses, we identified 12 compounds with broad-spectrum activity, and found a subset blocking viral internalisation and/or fusion. Importantly, we show that compounds identified with this approach can reduce viral replication in a mouse model of Zika infection. This work provides proof of concept that it is possible to identify broad-spectrum inhibitors by iterative phenotypic screenings, and that inhibition of host-pathways critical for viral life cycles can be an effective antiviral strategy.

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Manogepix (APX001A) Displays Potent In Vitro Activity against Human Pathogenic Yeast, but with an Unexpected Correlation to Fluconazole MICs

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00429-20 ◽

2020 ◽

Vol 64 (7) ◽

Cited By ~ 4

Author(s):

Maiken Cavling Arendrup ◽

Karin Meinike Jørgensen

Keyword(s):

Amphotericin B ◽

Broad Spectrum ◽

Hot Spot ◽

Its Sequencing ◽

Wild Type ◽

Pathogenic Yeast ◽

Fluconazole Resistance ◽

Content Type ◽

Spectrum Activity ◽

Broad Spectrum Activity

ABSTRACT Manogepix (APX001A) is the active moiety of the novel drug candidate fosmanogepix (APX001). We previously reported the broad-spectrum activity of manogepix but also observed a correlation between increased manogepix and fluconazole MICs. Here, we extended this study and included isolates with acquired fluconazole resistance. Isolates (n = 835) were identified using CHROMagar, matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS), and, when needed, internal transcribed spacer (ITS) sequencing. EUCAST E.Def 7.3.1 susceptibility testing included manogepix, amphotericin B, anidulafungin, micafungin, fluconazole, and voriconazole. Manogepix wild-type-upper-limit (WT-UL) values were established following EUCAST principles for the epidemiological cutoff value (ECOFF) setting allowing wild-type/non-wild-type classification. Drug-specific MIC correlations were investigated using Pearson’s correlation. Manogepix modal MICs were low (range, 0.004 to 0.06 mg/liter against 16/20 included species). Exceptions were Candida krusei and Candida inconspicua and, to a lesser extent, Candida kefyr and Pichia kluyveri. The activity was independent of Fks echinocandin hot spot alterations (n = 17). Adopting the WT-UL established for Candida albicans, Candida dubliniensis, Candida glabrata, Candida parapsilosis, and Candida tropicalis, 14/724 (1.9%) isolates were non-wild type for manogepix. Twelve of these (85.7%) were also non-wild type for fluconazole. A statistically significant correlation was observed between manogepix and fluconazole MICs for C. albicans, C. dubliniensis, C. glabrata, C. parapsilosis, and C. tropicalis (Pearson’s r = 0.401 to 0.575) but not between manogepix and micafungin or amphotericin B MICs for any species except C. tropicalis (r = 0.519 for manogepix versus micafungin). Broad-spectrum activity was confirmed for manogepix against contemporary yeast. However, a 1 to 4 2-fold dilutions increase in manogepix MICs is observed in a subset of isolates with acquired fluconazole resistance. Further studies on the potential underlying mechanism and implication for optimal dosing are warranted.

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