CLC-Pred: A freely available web-service for in silico prediction of human cell line cytotoxicity for drug-like compounds

Lagunin, Alexey; Dubovskaja, Varvara; Rudik, Anastasia V.; Pogodin, Pavel V.; Druzhilovskiy, Dmitry S.; Gloriozova, Tatyana A.; Филимонов, Д. А.; Sastry, Narahari G.; Poroikov, Vladimir

doi:10.1371/journal.pone.0191838

Cited by 141 publications

(103 citation statements)

References 45 publications

(41 reference statements)

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“…For each molecule, the Pa (probable activity) and Pi (probable inactivity) values, both ranging from 0,000 to 1,000, were reported. Higher values of Pa are associated with a higher probability to obtain that effect experimentally, although some real activities could be lost ( 44 ). The study reported only the cytostatic, cytotoxic and antimicrobial activities of the selected compounds, with a Pa>0,700.…”

Section: Methodsmentioning

confidence: 99%

The double effect of walnut septum extract (Juglans regia L.) counteracts A172 glioblastoma cell survival and bacterial growth

et al. 2020

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Walnut ( Juglans regia L.) is considered to be a 'superfood' for its multiple protective actions on human health. Walnut extracts have proven antitumor activity in different cancer cell lines. However, the efficacy of septum extract against glioblastoma has still not been investigated. Glioblastoma is the most difficult type of brain cancer to treat. The standard therapy, based on temozolomide, causes several side effects, including neutropenia and lymphocytopenia, which often favor the onset of opportunistic infections. In the present study, the chemical profile of the Sicilian walnut septum ethanolic extract was analyzed using high-performance liquid chromatography (HPLC)-diode array detection and HPLC-electrospray ionization tandem mass spectrometry. The potential cytostatic activity of the extract against the human A172 glioblastoma cell line was investigated and the results showed that the extract could decrease cancer cell proliferation and migration. Using cytofluorimetric analyses and caspase-3 assays, the pro-apoptotic action of walnut extract was demonstrated. Furthermore, the evaluation of the antibacterial activity high-lighted the efficacy of the extract in reducing Gram-positive and Gram-negative bacterial growth, most of which were resistant to the antibiotic, ciprofloxacin. Finally, Prediction of Activity Spectra for Substances analysis showed the predicted antitumor and antibacterial activity of HPLC detected compounds. The promising results could provide novel perspective in the field of chemotherapeutic co-adjuvants.

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Section: Methodsmentioning

confidence: 99%

The double effect of walnut septum extract (Juglans regia L.) counteracts A172 glioblastoma cell survival and bacterial growth

et al. 2020

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“…In silico cytotoxicity screening was performed by cell line cytotoxicity predictor (CLC-Pred) as per published protocol ( Lagunin et al, 2018 ).…”

Section: Methodsmentioning

confidence: 99%

Denovo designing, retrosynthetic analysis, and combinatorial synthesis of a hybrid antiviral (VTAR-01) to inhibit the interaction of SARS-CoV2 spike glycoprotein with human angiotensin-converting enzyme 2

Tiwari

2020

Biology Open

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SARS-like coronavirus (SARS-CoV2) has emerged as a global threat to humankind and is rapidly spreading. The infectivity, pathogenesis, and infection of this virus are dependent on the interaction of SARS-CoV2 spike protein with human ACE2 (hACE2). Spike protein contains a receptor-binding domain (RBD) that recognizes hACE-2. In the present study, we are reporting a denovo designed novel hybrid antiviral ‘VT-AR-01’ molecule that binds at the interface of RBD-hACE2 interaction. A series of antiviral molecules were tested for binding at the interface of RBD-hACE2 interaction. In-silico screening, molecular mechanics, molecular dynamics simulation (MDS) analysis suggest ribavirin, ascorbate, lopinavir, and hydroxychloroquine have strong interaction at RBD-hACE2 interface. These four molecules were used for denovo fragment-based antiviral design. Denovo designing, docking, and MDS analysis identified a ‘VTAR’ hybrid molecule that has better interaction with this interface as compared to all antiviral used to design it. We have further used retrosynthetic analysis and combinatorial synthesis to design 100 variants of VT-AR molecules. Retrosynthetic analysis and combinatorial synthesis, along with docking and MDS, identified VT-AR-01 that interact with the interface of the RBD-ACE2 complex. MDS analysis confirmed its interaction with the RBD-ACE2 interface by involving Glu35 and Lys353 of ACE2, as well as Gln493 and Ser494 of RBD. Interaction of spike protein with ACE2 is essential for pathogenesis and infection of this virus; hence, this in-silico designed hybrid antiviral molecule (VT-AR-01) that binds at the interface of RBD-hACE2 may be further developed to control the infection of SARS-CoV2.

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“…In-silico cytotoxicity screening was performed using online CLC-Pred (Cell line Cytotoxicity Predictor) as per published protocol ( Lagunin et al., 2018 ).…”

Section: Methodsmentioning

confidence: 99%

Novel hybrid antiviral VTRRT-13V2.1 against SARS-CoV2 main protease: retro-combinatorial synthesis and molecular dynamics analysis

Tiwari

2020

Heliyon

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The COVID-19 pandemic caused by SARS-CoV-2 has now emerged as a global health problem and is responsible for high mortality and morbidity. The SARS-CoV-2 main protease (M pro ) emerged as a promising drug target because of its essential role in the processing of polyproteins, which is translated from viral RNA. The present study reports a designed novel hybrid antiviral molecule (VTRRT-13.V2.1) against SARS-CoV2 main protease. A series of different combinations of hybrid antiviral were generated from nonspecific antiviral molecules currently used to control COVID-19. To enhance the specificity of the designed hybrid antiviral molecule, the core pocket region of the active site of M pro protein was targeted. In-silico screening, molecular mechanics, molecular dynamics simulation (MDS) analysis identified a hybrid VTRRT-13.V2 molecule. Retrosynthetic analysis and combinatorial synthesis generated 1000 analogs of VTRRT-13.V2 molecules. Docking, molecular mechanics, and MDS analysis selected VTRRT-13.V2.1 as a possible inhibitor for SARS-CoV2 main protease. Comparative analysis of all the results showed that VTRRT-13.V2.1 have the highest docking Glide score (-12.28 kcal/mol) and best binding energy (-52.23 kcal/mol) as compared to the other hybrid constructs such as VTRRT-13.V2 (-9.47 and -47.36 kcal/mol), VTRRT-13 (-8.9 and -47.55 kcal/mol), and current antiviral investigated. The mutational sensitivity screening showed that binding residues of M pro are not present in mutation hotspots. It was also observed that VTRRT-13.V2.1 does not have any human off-targets. SARS-CoV2 main protease is essential for the survival of this virus; hence, a designed novel hybrid antiviral molecule (VTRRT-13.V2.1) might be useful to control the infection of COVID-19 infection.

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CLC-Pred: A freely available web-service for in silico prediction of human cell line cytotoxicity for drug-like compounds

Cited by 141 publications

References 45 publications

The double effect of walnut septum extract (Juglans regia L.) counteracts A172 glioblastoma cell survival and bacterial growth

The double effect of walnut septum extract (Juglans regia L.) counteracts A172 glioblastoma cell survival and bacterial growth

Denovo designing, retrosynthetic analysis, and combinatorial synthesis of a hybrid antiviral (VTAR-01) to inhibit the interaction of SARS-CoV2 spike glycoprotein with human angiotensin-converting enzyme 2

Novel hybrid antiviral VTRRT-13V2.1 against SARS-CoV2 main protease: retro-combinatorial synthesis and molecular dynamics analysis

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