Medicines for Malaria Venture COVID Box: a source for repurposing drugs with antifungal activity against human pathogenic fungi

Almeida‐Paes, Rodrigo; Andrade, Iara Bastos de; Ramos, Mariana Lucy Mesquita; Rodrigues, Marcus; Nascimento, Vinícius Alves do; Bernardes-Engemann, Andréa Reis; Frasés, Susana

doi:10.1590/0074-02760210207

Cited by 15 publications

(14 citation statements)

References 47 publications

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“…The COVID Box was developed by the MMV in collaboration with scientists from industry and academia, to rapidly respond to the urgent need to combat COVID-19. As previously described, the COVID Box not only supports research against SARS-CoV-2, but also against other human threats [29,30]. However, this is the first study to evaluate the COVID Box against a human protozoan parasite.…”

Section: Discussionmentioning

confidence: 56%

Repurposing the Medicines for Malaria Venture’s COVID Box to discover potent inhibitors of Toxoplasma gondii, and in vivo efficacy evaluation of almitrine bismesylate (MMV1804175) in chronically infected mice

et al. 2023

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Toxoplasmosis, caused by the obligate intracellular parasite Toxoplasma gondii, affects about one-third of the world’s population and can cause severe congenital, neurological and ocular issues. Current treatment options are limited, and there are no human vaccines available to prevent transmission. Drug repurposing has been effective in identifying anti-T. gondii drugs. In this study, the screening of the COVID Box, a compilation of 160 compounds provided by the "Medicines for Malaria Venture" organization, was conducted to explore its potential for repurposing drugs to combat toxoplasmosis. The objective of the present work was to evaluate the compounds’ ability to inhibit T. gondii tachyzoite growth, assess their cytotoxicity against human cells, examine their absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties, and investigate the potential of one candidate drug through an experimental chronic model of toxoplasmosis. Early screening identified 29 compounds that could inhibit T. gondii survival by over 80% while keeping human cell survival up to 50% at a concentration of 1 μM. The Half Effective Concentrations (EC50) of these compounds ranged from 0.04 to 0.92 μM, while the Half Cytotoxic Concentrations (CC50) ranged from 2.48 to over 50 μM. Almitrine was chosen for further evaluation due to its favorable characteristics, including anti-T. gondii activity at nanomolar concentrations, low cytotoxicity, and ADMET properties. Administering almitrine bismesylate (Vectarion®) orally at dose of 25 mg/kg/day for ten consecutive days resulted in a statistically significant (p < 0.001) reduction in parasite burden in the brains of mice chronically infected with T. gondii (ME49 strain). This was determined by quantifying the RNA of living parasites using real-time PCR. The presented results suggest that almitrine may be a promising drug candidate for additional experimental studies on toxoplasmosis and provide further evidence of the potential of the MMV collections as a valuable source of drugs to be repositioned for infectious diseases.

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Section: Discussionmentioning

confidence: 56%

Repurposing the Medicines for Malaria Venture’s COVID Box to discover potent inhibitors of Toxoplasma gondii, and in vivo efficacy evaluation of almitrine bismesylate (MMV1804175) in chronically infected mice

et al. 2023

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“…Additionally, at least 14 non-antifungal drugs with potential activity against SARS-CoV-2 have shown in vitro antifungal activity against P . brasiliensis [ 18 ]. Therefore, this may also have contributed to protecting individuals against disease due to Paracoccidioides spp., which may perhaps explain, in part, the absence of post-COVID-19 PCM cases.…”

Section: Discussionmentioning

confidence: 99%

“…The patients from this study did not receive any drugs with known clinical activity against SARS-CoV-2, except favipravir, which does not have antifungal activity against Paracoccidioides spp. [ 18 ]…”

Section: Discussionmentioning

confidence: 99%

COVID-19 in patients with paracoccidioidomycosis

et al. 2023

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Introduction In 2020, we reported the first patient with concomitant COVID-19 and paracoccidioidomycosis (PCM). Since then, no other cases have been recorded in the literature. We aim to update information on the occurrence of COVID-19 in patients with PCM followed at a reference center for infectious diseases at Rio de Janeiro, Brazil. Methods We reviewed the medical records from patients diagnosed with PCM who presented with clinical symptoms, radiological findings, and/or laboratory diagnosis of COVID-19 at any time during their acute or follow-up care. The clinical profiles of these patients were described. Results Between March 2020 and September 2022, we identified six individuals with COVID-19 among the 117 patients with PCM evaluated. The median age was 38 years and the male to female ratio 2:1. Most patients (n = 5) presented for evaluation due to acute PCM. The severity of COVID-19 ranged from mild to severe in acute PCM and only the single patient with chronic PCM died. Conclusions There is a range of disease severity in COVID-19 and PCM co-infection and concomitant disease may represent a severe association, especially in the chronic type of the mycosis with pulmonary involvement. As COVID-19 and chronic PCM share similar clinical aspects and PCM is neglected, it is probable that COVID-19 has been hampering simultaneous PCM diagnosis, which can explain the absence of new co-infection reports. With the continued persistence of COVID-19 globally, these findings further suggest that more attention by providers is necessary to identify co-infections with Paracoccidioides.

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“…This approach gains particular significance in the current global context, with the world grappling with the COVID-19 pandemic, which has propelled the search for potent antiviral agents. Initiatives such as the COVID Box have surfaced in response to this pressing demand, offering a curated collection of 160 potential drug candidates ( Almeida-Paes et al, 2021 ). These compounds encompass a range of bioactivities, each demonstrating activity or suspected activity against SARS-CoV-2, the virus responsible for the ongoing pandemic.…”

Section: Introductionmentioning

confidence: 99%

Exploring therapeutic approaches against Naegleria fowleri infections through the COVID box

Chao-Pellicer,

Arberas-Jiménez,

Sifaoui

et al. 2024

International Journal for Parasitology: Drugs and Drug Resistan

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Medicines for Malaria Venture COVID Box: a source for repurposing drugs with antifungal activity against human pathogenic fungi

Cited by 15 publications

References 47 publications

Repurposing the Medicines for Malaria Venture’s COVID Box to discover potent inhibitors of Toxoplasma gondii, and in vivo efficacy evaluation of almitrine bismesylate (MMV1804175) in chronically infected mice

Repurposing the Medicines for Malaria Venture’s COVID Box to discover potent inhibitors of Toxoplasma gondii, and in vivo efficacy evaluation of almitrine bismesylate (MMV1804175) in chronically infected mice

COVID-19 in patients with paracoccidioidomycosis

Exploring therapeutic approaches against Naegleria fowleri infections through the COVID box

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