The application of in silico experimental model in the assessment of ciprofloxacin and levofloxacin interaction with main SARS-CoV-2 targets: S-, E- and TMPRSS2 proteins, RNA-dependent RNA polymerase and papain-like protease (PLpro)—preliminary molecular docking analysis

Marciniec, Krzysztof; Beberok, Artur; Boryczka, Stanisław; Wrześniok, Dorota

doi:10.1007/s43440-021-00282-8

Cited by 6 publications

(3 citation statements)

References 37 publications

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“…In the presence of chloroquine, the viral spike protein is no longer able to link gangliosides [59]. Chloroquine also interacts with the TMPRSS2 protein [51,64,65]. The replicase 3CLpro may also be a potential target for chloroquine [51,55,66,67].…”

Section: Discussionmentioning

confidence: 99%

Antiviral Activity of Repurposing Ivermectin against a Panel of 30 Clinical SARS-CoV-2 Strains Belonging to 14 Variants

et al. 2022

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Over the past two years, several variants of SARS-CoV-2 have emerged and spread all over the world. However, infectivity, clinical severity, re-infection, virulence, transmissibility, vaccine responses and escape, and epidemiological aspects have differed between SARS-CoV-2 variants. Currently, very few treatments are recommended against SARS-CoV-2. Identification of effective drugs among repurposing FDA-approved drugs is a rapid, efficient and low-cost strategy against SARS-CoV-2. One of those drugs is ivermectin. Ivermectin is an antihelminthic agent that previously showed in vitro effects against a SARS-CoV-2 isolate (Australia/VI01/2020 isolate) with an IC50 of around 2 µM. We evaluated the in vitro activity of ivermectin on Vero E6 cells infected with 30 clinically isolated SARS-CoV-2 strains belonging to 14 different variants, and particularly 17 strains belonging to six variants of concern (VOC) (variants related to Wuhan, alpha, beta, gamma, delta and omicron). The in vitro activity of ivermectin was compared to those of chloroquine and remdesivir. Unlike chloroquine (EC50 from 4.3 ± 2.5 to 29.3 ± 5.2 µM) or remdesivir (EC50 from 0.4 ± 0.3 to 25.2 ± 9.4 µM), ivermectin showed a relatively homogeneous in vitro activity against SARS-CoV-2 regardless of the strains or variants (EC50 from 5.1 ± 0.5 to 6.7 ± 0.4 µM), except for one omicron strain (EC50 = 1.3 ± 0.5 µM). Ivermectin (No. EC50 = 219, mean EC50 = 5.7 ± 1.0 µM) was, overall, more potent in vitro than chloroquine (No. EC50 = 214, mean EC50 = 16.1 ± 9.0 µM) (p = 1.3 × 10−34) and remdesivir (No. EC50 = 201, mean EC50 = 11.9 ± 10.0 µM) (p = 1.6 × 10−13). These results should be interpreted with caution regarding the potential use of ivermectin in SARS-CoV-2-infected patients: it is difficult to translate in vitro study results into actual clinical treatment in patients.

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Section: Discussionmentioning

confidence: 99%

Antiviral Activity of Repurposing Ivermectin against a Panel of 30 Clinical SARS-CoV-2 Strains Belonging to 14 Variants

et al. 2022

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“…10), while CQ had no H-bond in the hydrophobic pocket. Other studies also showed a better binding affinity of HCQ with TMPRSS2 than that of CQ [9,10] .…”

Section: : Cq and Hcq Interaction Types And Modes With Tnf Gapdh Lck ...mentioning

confidence: 96%

An Integrated Strategy Designed To Explore the Common and Diverging Mechanisms of Potential Drugs against the Novel Coronavirus Pneumonia Based on Network Pharmacology and In Silico Molecular Docking Technology

Zhao¹,

Li²,

Zheng³

et al. 2022

IJPS

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Zhao et al.: Strategy for Study Common and Diverging Mechanisms of Drugs to Coronavirus Disease 2019Drug repositioning may be a promising way to find potential therapies against coronavirus disease 2019. Although chloroquine and hydroxychloroquine showed controversial results against the coronavirus disease 2019 disease, the potential common and diverging mechanisms of action are not reported and need to be dissected for better understanding them. An integrated strategy was proposed to systematically decipher the common and diverging aspects of mechanism of chloroquine and hydroxychloroquine against coronavirus disease 2019-disease network based on network pharmacology and in silico molecular docking. Potential targets of the two drugs and coronavirus disease 2019 related genes were collected from online public databases. Target function enrichment analysis, tissue enrichment maps and molecular docking analysis were carried out to facilitate the systematic understanding of common and diverging mechanisms of the two drugs. Our results showed that 51 chloroquine targets and 47 hydroxychloroquine targets were associated with coronavirus disease 2019. The core targets include tumor necrosis factor, glyceraldehyde 3-phosphate dehydrogenase, lymphocyte-specific protein-tyrosine kinase, beta-2 microglobulin, nuclear receptor coactivator 1, peroxisome proliferator-activated receptor gamma and glutathione disulfide reductase. Both chloroquine and hydroxychloroquine had good binding affinity towards tumor necrosis factor (affinity=-8.6 and -8.4 kcal/mol, respectively) and glyceraldehyde 3-phosphate dehydrogenase (-7.5 and -7.5 kcal/mol). Chloroquine and hydroxychloroquine both had good affinity with angiotensinconverting enzyme 2, 3-chymotrypsin-like protease and transmembrane serine protease 2. However, hydroxychloroquine manifested better binding affinity with the three proteins comparing with that of chloroquine. Chloroquine and hydroxychloroquine could have potential to inhibit over-activated immunity and inflammation. The potential tissue-specific regulation of the two drugs against severe acute respiratory syndrome coronavirus 2 infection may related with the lung, liver, brain, placenta, kidney, blood, eye, etc. In conclusion, our data systematically demonstrated chloroquine and hydroxychloroquine may have potential regulatory effects on coronavirus disease 2019 disease network, which may affect multiple organs, protein targets and pathways. Routine measurements of the chloroquine and hydroxychloroquine blood concentrations and tailored therapy regimen may be essential. But, further rigorous and high quality randomized controlled clinical trials are warranted to validate the antiviral effects of chloroquine and hydroxychloroquine against severe acute respiratory syndrome coronavirus 2. Our proposed strategy could facilitate the drug repurposing efforts for coronavirus disease 2019 treatment.

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“…Additionally, using molecular docking, it was shown how levooxacin attaches to several SARS-CoV-2 proteins (E and TMPRSS2 proteins, PLpro protease, and RNA-dependent RNA polymerase). 19 Also, LVX has various immunomodulatory effects that attenuate the inammatory response by inhibiting pro-inammatory cytokines. 20 Many countries reported COVID-19 treatment protocols using RDV and HCQ for hospitalized patients.…”

Section: Scientistsmentioning

confidence: 99%

A validated eco-friendly HPLC-FLD for analysis of the first approved antiviral remdesivir with other potential add-on therapies for COVID-19 in human plasma and pharmaceuticals

Taha,

Hassan,

Elmasry

et al. 2023

Anal. Methods

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The application of in silico experimental model in the assessment of ciprofloxacin and levofloxacin interaction with main SARS-CoV-2 targets: S-, E- and TMPRSS2 proteins, RNA-dependent RNA polymerase and papain-like protease (PLpro)—preliminary molecular docking analysis

Cited by 6 publications

References 37 publications

Antiviral Activity of Repurposing Ivermectin against a Panel of 30 Clinical SARS-CoV-2 Strains Belonging to 14 Variants

Antiviral Activity of Repurposing Ivermectin against a Panel of 30 Clinical SARS-CoV-2 Strains Belonging to 14 Variants

An Integrated Strategy Designed To Explore the Common and Diverging Mechanisms of Potential Drugs against the Novel Coronavirus Pneumonia Based on Network Pharmacology and In Silico Molecular Docking Technology

A validated eco-friendly HPLC-FLD for analysis of the first approved antiviral remdesivir with other potential add-on therapies for COVID-19 in human plasma and pharmaceuticals

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