New in silico insights into the application of the (hydroxy)chloroquine with macrolide antibiotics co-crystals against the SARS-CoV-2 virus

Castro, Alexandre A. de; Assis, Letícia C.; Ramalho, Teodorico C.; Porta, Felipe A. La

doi:10.21203/rs.3.rs-66640/v1

Cited by 5 publications

(7 citation statements)

References 31 publications

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“…37 As a result, it is important to note that the values extracted from RMSD (5R82 = 0.94 Ǻ / 3H5Y = 1.55 Ǻ) showed that the program used in this study is adequate for predicting the conformation that the co-crystallized ligands adopted experimentally within the viral M pro and RdRp of SARS-CoV-2. 12,13,38 The re-docking con gurations were maintained to perform the docking calculations of the drugs investigated as well as their metabolism fragments. All computed interaction energy results are exhibited in Table 1.…”

Section: Docking Results and Admetmentioning

confidence: 99%

“…36 The crystallographic M pro and RdRp structures used in this simulations were prepared according to our previous studies. 12,13,39 Based on this strategy, we also investigate the absorption, distribution, mechanism, excretion, and toxicity (ADMET) properties for antiviral target drugs and their by-products metabolic. Thereby, the acute toxicity and other relevant pharmacokinetics parameters can easily be obtained from a rat model-based admetSAR predictor (http://biosig.unimelb.edu.au/pkcsm/prediction).…”

Section: Computational Models and Methodsmentioning

confidence: 99%

“…This ADMET procedure has been used previously in similar systems with large success. 12,13,38 Declarations Figures…”

Section: Computational Models and Methodsmentioning

confidence: 99%

“…Possible candidates for the treatment of COVID-19 include the antiviral drugs Favipiravir, Galidesivir, Nitazoxanide, Remdesivir, Ribavirin, Chloroquine, and Hydroxychloroquine due to their ability for the enzymatic inhibition of SARS-CoV-2. [7][8][9][10][11][12][13] In addition to the effectiveness of a particular drug in the treatment of a disease, drug design must also consider xenobiotics, or the mechanism via which the by-products of a medicine interact with and exit the human body. [14][15][16][17] As is well known, the general mechanism of xenobiotics involves three main phases: Phase I, drug activation through oxidation, reduction, and hydrolysis; Phase II, drug inactivation by means of conjugation with proteins to yield water-soluble metabolites that can be eliminated from the body; and Phase III, biotransformation by enzymes before the waste leaves the body.…”

Section: Introductionmentioning

confidence: 99%

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Effect of drug metabolism in the treatment of SARS-CoV-2 from an entirely computational perspective

Jesus

Assis

et al. 2021

Preprint

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Understanding the effects of metabolism on the rational design of novel and more effective drugs is still a considerable challenge. To the best of our knowledge, there are no entirely computational strategies that make it possible to predict these effects. From this perspective, the development of such methodologies could contribute to significantly reduce the side effects of medicines, leading to the emergence of more effective and safer drugs. Thereby, in this study, our strategy is based on simulating the electron ionization mass spectrometry (EI-MS) fragmentation of the drug molecules and combined with molecular docking and ADMET models in two different situations. In the first model, the drug is docked without considering the possible metabolic effects. In the second model, each of the intermediates from the EI-MS results is docked, and metabolism occurs before the drug accesses the biological target. As a proof of concept, in this work, we investigate the main antiviral drugs used in clinical research to treat COVID-19. As a result, our strategy made it possible to assess the biological activity and toxicity of all potential by-products. We believed that our findings provide new chemical insights that can benefit the rational development of novel drugs in the future.

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Section: Docking Results and Admetmentioning

confidence: 99%

Section: Computational Models and Methodsmentioning

confidence: 99%

“…This ADMET procedure has been used previously in similar systems with large success. 12,13,38 Declarations Figures…”

Section: Computational Models and Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Effect of drug metabolism in the treatment of SARS-CoV-2 from an entirely computational perspective

Jesus

Assis

et al. 2021

Preprint

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“…2,[16][17][18] Due to the eminent urgency to fight this COVID-19 outbreak, researchers around the world have widely evaluated the effectiveness of diverse approved antiviral agents for this proposed. [1][2][3][19][20][21] Among these approved drugs, in particular, favipiravir (also known as T-705) is a compound analogous to guanine, which was developed with satisfactory activity against many RNA-polymerase viruses (e.g., Ebola, chikungunya, yellow fever, influenza, norovirus and enterovirus), [22][23][24][25][26][27] showed good clinical efficacy against coronavirus. 28,29 Although the highly mobile protons in the structure of favipiravir compounds has allowed for their tautomeric forms, 30 the interpretation of the spectroscopic properties of the tautomers has proven to be highly complex and difficult.…”

mentioning

confidence: 99%

Theoretical Insights into the Effect of Halogenated Substituent on the Electronic Structure and Spectroscopic Properties of the Favipiravir Tautomeric Forms and Its Implications on the Treatment of COVID-19

Assis¹,

Castro²,

Jesus³

et al. 2020

Preprint

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<p>In this study, we systematically investigated the electronic structure, spectroscopic (nuclear magnetic resonance, infrared, Raman, electron ionization mass spectrometry, UV-Vis, circular dichroism, and emission) properties, and tautomerism of halogenated favipiravir compounds (fluorine, chlorine, and bromine) from a computational perspective. Additionally, the effects of hydration on the proton transfer mechanism of the tautomeric forms of the halogenated favipiravir compounds are discussed. Our results suggest that spectroscopic properties allow for the elucidation of such tautomeric forms. As is well-known, the favipiravir compound has excellent antiviral properties and hence was recently tested for the treatment of new coronavirus (SARS-CoV-2). Through in silico modeling, in the current study, we evaluate the role of such tautomeric forms in order to consider the effect of drug-metabolism into the inhibition process of the main protease (M<sup>pro</sup>) and RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 virus. These findings clearly indicated that all title compounds are better as RNA-inhibiting.</p>

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Differential evolution and particle swarm optimization against COVID-19

Piotrowski

Piotrowska

2021

Artif Intell Rev

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COVID-19 disease, which highly affected global life in 2020, led to a rapid scientific response. Versatile optimization methods found their application in scientific studies related to COVID-19 pandemic. Differential Evolution (DE) and Particle Swarm Optimization (PSO) are two metaheuristics that for over two decades have been widely researched and used in various fields of science. In this paper a survey of DE and PSO applications for problems related with COVID-19 pandemic that were rapidly published in 2020 is presented from two different points of view: 1. practitioners seeking the appropriate method to solve particular problem, 2. experts in metaheuristics that are interested in methodological details, inter comparisons between different methods, and the ways for improvement. The effectiveness and popularity of DE and PSO is analyzed in the context of other metaheuristics used against COVID-19. It is found that in COVID-19 related studies: 1. DE and PSO are most frequently used for calibration of epidemiological models and image-based classification of patients or symptoms, but applications are versatile, even interconnecting the pandemic and humanities; 2. reporting on DE or PSO methodological details is often scarce, and the choices made are not necessarily appropriate for the particular algorithm or problem; 3. mainly the basic variants of DE and PSO that were proposed in the late XX century are applied, and research performed in recent two decades is rather ignored; 4. the number of citations and the availability of codes in various programming languages seems to be the main factors for choosing metaheuristics that are finally used.

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New in silico insights into the application of the (hydroxy)chloroquine with macrolide antibiotics co-crystals against the SARS-CoV-2 virus

Cited by 5 publications

References 31 publications

Effect of drug metabolism in the treatment of SARS-CoV-2 from an entirely computational perspective

Effect of drug metabolism in the treatment of SARS-CoV-2 from an entirely computational perspective

Theoretical Insights into the Effect of Halogenated Substituent on the Electronic Structure and Spectroscopic Properties of the Favipiravir Tautomeric Forms and Its Implications on the Treatment of COVID-19

Differential evolution and particle swarm optimization against COVID-19

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