Drug repositioning is an alternative for the treatment of coronavirus COVID-19

Serafin, Marissa Bolson; Bottega, Angelita; Foletto, Vitória Segabinazzi; Rosa, Taciéli Fagundes da; Hörner, Andreas; Hörner, Rosmari

doi:10.1016/j.ijantimicag.2020.105969

Cited by 110 publications

(98 citation statements)

References 19 publications

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“…Repurposing drugs already in clinical use is the most practical approach for the rapid identification of antivirals for COVID -19, given the urgency and severity of the pandemic 14,15 . Remdesivir, a broad-spectrum antiviral drug, has been reported to show efficacy against SARS-CoV-2 16 .…”

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confidence: 99%

Metallodrug ranitidine bismuth citrate suppresses SARS-CoV-2 replication and relieves virus-associated pneumonia in Syrian hamsters

et al. 2020

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Selected metallo-compounds exhibit potent activity against SARS-CoV-2 in vitro. Historically, metal compounds have been used as antimicrobial agents. However, their antiviral activities have not been explored extensively. Our earlier studies demonstrated that bismuth drugs and related compounds exhibit excellent antiviral activity against SARS-CoV 21. Building on these results, we selected six metal compounds-two bismuth(iii) citrate-based drugs (colloidal bismuth subcitrate (CBS) and RBC, two bismuth(iii) porphyrins (Bi(TPP) (TPP, tetraphenylporphyrinate) and Bi(TPyP) (TPyP, tetra(4-pyridyl)porphyrin)), one Au(i)-based drug (Auranofin), as well as its active derivative, chloro(triethylphosphine) gold(i) (Au(PEt 3)Cl)-to carry out a primary evaluation against SARS-CoV-2 in vitro (Extended Data Fig. 1). The 50% cytotoxicity concentrations (CC 50) of these compounds in monkey kidney Vero E6 cells were determined to be 3,254 ± 21 μM for CBS, 2,243 ± 43 μM for RBC, >400 μM for both Bi(TPP) and Bi(TPyP), 14.2 ± 1.3 μM for auranofin and 13.5 ± 1.8 μM for Au(PEt 3)Cl (Extended Data Fig. 2). The four bismuth(iii) compounds were prioritized for further evaluation of their CC 50 values in human colorectal Caco-2 cells because of their promisingly low cytotoxicity compared with the Au(i)-based drugs, resulting in similar CC 50 values ranging from 400 to 3,740 μM (Extended Data Fig. 2). To evaluate their antiviral potency, the half-maximal effective doses (EC 50) of the bismuth(iii) compounds were determined at low micromolar levels as 4.6 ± 0.4 µM for CBS, 2.3 ± 0.5 µM for RBC, 3.9 ± 1.2 µM for Bi(TPP) and 7.5 ± 0.9 µM for Bi(TPyP). Remarkably, addition of all four bismuth(iii) compounds at 1 h post infection (h.p.i.) reduced viral RNA loads in both Vero E6 and Caco-2 cells in a dose-dependent manner (Fig. 1). In non-toxic concentrations, CBS and RBC exhibited more potent anti-SARS-CoV-2 activity than Bi(TPP) and Bi(TPyP), as evidenced by the maximal ~2-log versus 1-log viral load reduction in the Vero E6 cell lysate (Fig. 1a-d), ~3-log versus ~2-log reduction in the Caco-2 cell lysate (Fig. 1e-h), ~4-log versus ~3-log reduction in the Vero E6 cell culture supernatant (Fig. 1i-l) and ~4-log versus ~3-log reduction in the Caco-2 cell culture supernatant (Fig. 1m-p). Importantly, bismuth(iii) drugs/compounds greatly inhibited SARS-CoV-2, as evidenced by the markedly decreased expression of viral nucleoprotein in the drug-treated cells when compared with the dimethyl sulfoxide (DMSO)-treated group (Fig. 2a-f). To investigate which steps of the SARS-CoV-2 replication cycle were interrupted by the selected drug compounds, we performed a time-of-drug-addition assay by treating virus-infected cells with each compound at different time points, followed by measurements of viral titre after 9 h.p.i., when the first round of progeny virions were detectable in the cell culture supernatant. (Fig. 2g,h). Intriguingly, addition of Bi(TPyP) during pre-treatment or co-incubation of cells significantly suppressed virus replication, whereas n...

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Metallodrug ranitidine bismuth citrate suppresses SARS-CoV-2 replication and relieves virus-associated pneumonia in Syrian hamsters

et al. 2020

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“…The suggested model is an extremely efficient method to develop a group of sample candidate drugs using RNN model with BA which is applied to optimize the model parameters of RNN and then using the corona virus as a target, bind all the sample candidate drugs to it and find out the one with the best binding affinity. The drug with the best binding affinity will be a potential cure for the virus (Tang et al, 2020;Serafin et al, 2020;Shaha et al, 2020;Perricone et al, 2020). To the suggested algorithm steps are summarized in four main phases: (a) data preparation phase, (b) hyper-parameters optimizing phase, (c) learning phase, (d) fine-tuning for specific ligand subsets.…”

Section: The Proposed Model For Covid-19 Drugmentioning

confidence: 99%

Bat-inspired Optimizer for Prediction of Anti-Viral Cure Drug of SARS-CoV-2 based on Recurrent Neural Network

Elansary¹,

Hamdy²,

Darwish³

et al. 2020

JSMS

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COVID-19 is a large family of viruses that causes diseases ranging from the common cold to more severe diseases such as SARS-CoV. There are currently several attempts to create an anti-viral drug to combat the virus. The antiviral medicines could be promising treatment choices for COVID-19. Therefore, a fast strategy for drugs application that can be utilized to the patient immediately is necessary. In this context, deep learning-based architectures can be considered for predicting drug-target interactions accurately. This is due to a large amount of complicated knowledge, such as hydrophobic interactions, ionic interactions, and bonding with hydrogen. In this paper, Recurrent Neural Network (RNN) is used to build drug-target interaction prediction model to predict drug-target interactions. Bat Algorithm (BA) is used in this paper to optimize the model parameters of RNN (RNN-BA) and then using the corona virus as a target. The drug with the best binding affinity will be a potential cure for the virus. The proposed model consists of different four phases; data preparation phase, hyper-parameters optimizing phase, learning phase and fine-tuning for specific ligand subsets. The used dataset in this paper to train and evaluate the proposed model is selected from a total of 677,044 SMILES. The experimental results of the proposed model showed high level of performance in comparison with the related approaches.

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“…In such critical and desperate situations, physicians are faced with the challenge to take difficult decisions but always with the best interests of the patients in the fore [4,5]. Unfortunately, there is currently no widely accepted standard of care in the pharmacologic management of patients with COVID-19 [6] and repurposing of existing drugs [7] seems to be the only plausible option for the majority of the worldwide population with scarce resources.…”

Section: Introductionmentioning

confidence: 99%

Nitazoxanide against COVID-19 in three explorative scenarios

Calderón

Flores

Coria

et al. 2020

J Infect Dev Ctries

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Introduction: Nitazoxanide has shown efficacy in vitro against coronavirus infections (MERS, SARS, SARS-CoV-2). The aim of this report is to describe the results of treating COVID-19 positive patients with nitazoxanide in three clinical settings: pregnancy/puerperium, hospitalized patients in an Internal Medicine Service and in an ambulatory setting. Methodology: This was a prospective follow-up and report of COVID-19 cases in three different situations, pregnant women, hospitalized patients receiving medical attention in an Internal Medicine Service and ambulatory patients residing in Toluca City, and Mexico City. Results: The experience with a first group of 20 women, pregnant (17) or in immediate puerperium (3) was successful in 18 cases with two unfortunate deaths. The five cases treated in an Internal Medicine service showed a positive outcome with two patients weaned from mechanical ventilation. Of the remaining 16 patients treated in an ambulatory setting, all got cured. Nitazoxanide seems to be useful against SARS-CoV-2, not only in an early intervention but also in critical condition as well as in pregnancy without undesired effects for the babies. As an adjunctive therapy budesonide was used that seems to contribute to the clinical improvement. Conclusions: Nitazoxanide could be useful against COVID-19 as a safe and available regimen to be tested in a massive way immediately.

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Drug repositioning is an alternative for the treatment of coronavirus COVID-19

Cited by 110 publications

References 19 publications

Metallodrug ranitidine bismuth citrate suppresses SARS-CoV-2 replication and relieves virus-associated pneumonia in Syrian hamsters

Metallodrug ranitidine bismuth citrate suppresses SARS-CoV-2 replication and relieves virus-associated pneumonia in Syrian hamsters

Bat-inspired Optimizer for Prediction of Anti-Viral Cure Drug of SARS-CoV-2 based on Recurrent Neural Network

Nitazoxanide against COVID-19 in three explorative scenarios

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