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Fig 1.

(A): Ramachandran plot. SARS-CoV-2 RdRp (pdb: 6M71) protein and (B): Interfaces summary of SARS-CoV-2 RdRp (pdb: 6M71).

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Fig 1 Expand

Table 1.

Predicted antiviral activities (% inhibition) of cytidine derivatives 2–15, remdesivir, and AZT.

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Table 1 Expand

Fig 2.

Structures.

The designed cytidine (1) and its derivatives (2–15).

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Fig 2 Expand

Fig 3.

MESP map.

Cytidine (1) and its derivatives (2–15).

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Fig 3 Expand

Fig 4.

Binding conformation.

Interactions of control molecule with the enzyme.

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Fig 4 Expand

Fig 5.

Chemical interactions.

Derivatives (13) with the active site of SARS-CoV-2 (PDB: 6M71) were performed by Discovery Studio.

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Fig 5 Expand

Fig 6.

(A) Docked 3D pose. Derivative 13 with RdRp (PDB: 6M71). (B) The close viewer of key active site residues involved in interactions with derivative 13.

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Fig 6 Expand

Table 2.

The binding energy of the cytidine derivatives against RdRp.

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Table 2 Expand

Fig 7.

Backbone structural deviations.

Analysis based on molecular dynamics simulations. A. RMSD, B. RMSF and C. RoG.

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Fig 7 Expand

Fig 8.

Molecular dynamic simulation.

Snapshots of compound 13 with the enzyme at different nanoseconds.

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Fig 8 Expand

Table 3.

Prediction in silico of absorption of cytidine derivatives.

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Table 3 Expand

Fig 9.

Bioactivity radar.

Charts of the cytidine derivatives where FLEX: Flexibility, LIPO: Lipophilicity, INSATU: Unsaturation. and INSOLU: Insolubility.

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Fig 9 Expand

Table 4.

Determination of drug-likeness score of cytidine derivatives through Molinspiration cheminformatics online server.

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Table 4 Expand

Table 5.

Data of QSAR.

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Table 5 Expand

Fig 10.

Determination of drug-likeness.

Score of cytidine derivatives (1–15) through Osiris cheminformatics online server.

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Fig 10 Expand

Fig 11.

Comparison.

Toxicity risks and drug score calculations of compounds 1–15.

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Fig 11 Expand

Fig 12.

Atomic charge.

Calculations of compounds 1–15.

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Fig 12 Expand

Fig 13.

Identification.

Antifungal/antiviral pharmacophore site of compound 4 [6975].

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Fig 13 Expand