Nullscript inhibits Cryptosporidium and Toxoplasma growth

Murakoshi, Fumi; Bando, Hironori; Sugi, Tatsuki; Adeyemi, Oluyomi Stephen; Nonaka, Motohiro; Nakaya, Takaaki; Kato, Koichiro

doi:10.1016/j.ijpddr.2020.10.004

Cited by 13 publications

(6 citation statements)

References 26 publications

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“…Very little is known about epigenetic regulation in Cryptosporidium , but the C . parvum genome encodes histone modification enzymes [ 64 ], and the parasites are susceptible to pharmacological inhibition of these pathways [ 65 , 66 ].…”

Section: Discussionmentioning

confidence: 99%

Live imaging of the Cryptosporidium parvum life cycle reveals direct development of male and female gametes from type I meronts

et al. 2022

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Cryptosporidium is a leading infectious cause of diarrhea around the world associated with waterborne outbreaks, community spread, or zoonotic transmission. The parasite has significant impact on early childhood mortality, and infection is both a consequence and cause of malnutrition and stunting. There is currently no vaccine, and treatment options are very limited. Cryptosporidium is a member of the Apicomplexa, and, as typical for this, protist phylum relies on asexual and sexual reproduction. In contrast to other Apicomplexa, including the malaria parasite Plasmodium, the entire Cryptosporidium life cycle unfolds in a single host in less than 3 days. Here, we establish a model to image life cycle progression in living cells and observe, track, and compare nuclear division of asexual and sexual stage parasites. We establish the length and sequence of the cell cycles of all stages and map the developmental fate of parasites across multiple rounds of invasion and egress. We propose that the parasite executes an intrinsic program of 3 generations of asexual replication, followed by a single generation of sexual stages that is independent of environmental stimuli. We find no evidence for a morphologically distinct intermediate stage (the tetraploid type II meront) but demonstrate direct development of gametes from 8N type I meronts. The progeny of each meront is collectively committed to either asexual or sexual fate, but, importantly, meronts committed to sexual fate give rise to both males and females. We define a Cryptosporidium life cycle matching Tyzzer’s original description and inconsistent with the coccidian life cycle now shown in many textbooks.

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Section: Discussionmentioning

confidence: 99%

Live imaging of the Cryptosporidium parvum life cycle reveals direct development of male and female gametes from type I meronts

et al. 2022

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“…Nitazoxanide was used as a standard comparative drug. In vitro inhibition assays were carried out as previously described [22,23]. Briefly, oocysts were suspended in 1 ml of 0.1% sodium hypochlorite in PBS, incubated for 5 min at 4˚C, centrifuged for 10 min at 3000 rpm, and washed three times in PBS.…”

Section: Plos Neglected Tropical Diseasesmentioning

confidence: 99%

Identification of potent anti-Cryptosporidium new drug leads by screening traditional Chinese medicines

et al. 2022

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Cryptosporidium spp. are gastrointestinal opportunistic protozoan parasites that infect humans, domestic animals, and wild animals all over the world. Cryptosporidiosis is the second leading infectious diarrheal disease in infants less than 5 years old. Cryptosporidiosis is a common zoonotic disease associated with diarrhea in infants and immunocompromised individuals. Consequently, cryptosporidiosis is considered a serious economic, veterinary, and medical concern. The treatment options for cryptosporidiosis are limited. To address this problem, we screened a natural product library containing 87 compounds of Traditional Chinese Medicines for anti-Cryptosporidium compounds that could serve as novel drug leads and therapeutic targets against C. parvum. To examine the anti-Cryptosporidium activity and half-maximal inhibitory doses (EC50) of these compounds, we performed in vitro assays (Cryptosporidium growth inhibition assay and host cell viability assay) and in vivo experiments in mice. In these assays, the C. parvum HNJ-1 strain was used. Four of the 87 compounds (alisol-A, alisol-B, atropine sulfate, and bufotalin) showed strong anti-Cryptosporidium activity in vitro (EC50 values = 122.9±6.7, 79.58±13.8, 253.5±30.3, and 63.43±18.7 nM, respectively), and minimum host cell cytotoxicity (cell survival > 95%). Furthermore, atropine sulfate (200 mg/kg) and bufotalin (0.1 mg/kg) also showed in vivo inhibitory effects. Our findings demonstrate that atropine sulfate and bufotalin are effective against C. parvum infection both in vitro and in vivo. These compounds may, therefore, represent promising novel anti-Cryptosporidium drug leads for future medications against cryptosporidiosis.

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“…As for the treatment of C. parvum infection, it does not have an effective treatment directly, except for (NTZ) Nitazoxanide which is proven by the World Health Organization, but it is not effective for people with immunodeficiency, and many anti-Cryptosporidiosis compounds have been used, but they did not give positive results. Effective and did not kill the Oocyst permanently in a record time, including Metronidazole, Azithromycin, Paromomycin [7] ISSN: 2583-4053 Volume-1 Issue- From recent studies, Nullscript was identified as a compound that has a growth inhibitory effect, and was less toxic to host cells, Nullscript was able to significantly reduce the release of Oocyst in mice infected with C. parvum [8]…”

Section: Introductionmentioning

confidence: 99%

Therapeutic Comparison Between Alcoholic and Aqueous Plant Extract of Tannins with Metronidazole in Experimentally Infected Laboratory Mice Cryptosporidium parvum Oocysts

S.N.

Alkhashab

2022

JRASB

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The current study was conducted during the period between from the beginning of October 2021 until the end of March 2022. The aim of the study was to measure the therapeutic efficacy of alcoholic and aqueous extracts from the local tannins Cupressus sempervirens for the treatment of experimental infected laboratory mice with Cryptosporidiosis. Through a significant decrease in the number of Oocyst of the parasite that causes infection Cryptosporidium parvum after oral administration of the aqueous and alcoholic extracts with three concentrations (2, 1.3, 1) mg/ml compared to MTZ drug, as the alcoholic extract proved its efficacy by stopping the shedding of parasite Oocyst at the ninth day of treatment with its total absence on the eleventh day of treatment, while the shedding of parasite Oocysts in the group treated with aqueous extract stopped on the eleventh day and completely absent on the thirteenth day of infection.

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Nullscript inhibits Cryptosporidium and Toxoplasma growth

Cited by 13 publications

References 26 publications

Live imaging of the Cryptosporidium parvum life cycle reveals direct development of male and female gametes from type I meronts

Live imaging of the Cryptosporidium parvum life cycle reveals direct development of male and female gametes from type I meronts

Identification of potent anti-Cryptosporidium new drug leads by screening traditional Chinese medicines

Therapeutic Comparison Between Alcoholic and Aqueous Plant Extract of Tannins with Metronidazole in Experimentally Infected Laboratory Mice Cryptosporidium parvum Oocysts

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