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Quantitative Biology

ISSN 2095-4689

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Quant. Biol.    2021, Vol. 9 Issue (4) : 440-450    https://doi.org/10.15302/J-QB-021-0263
RESEARCH ARTICLE
Molecular docking of cyanine and squarylium dyes with SARS-CoV-2 proteases NSP3, NSP5 and NSP12
Pavel Pronkin(), Alexander Tatikolov
N.M. Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, Moscow 119991, Russia
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Abstract

Background: The outbreak and continued spread of coronavirus infection (COVID-19) sets the goal of finding new tools and methods to develop analytical procedures and tests to detect, study infection and prevent morbidity.

Methods: The noncovalent binding of cyanine and squarylium dyes of different classes (60 compounds in total) with the proteases NSP3, NSP5, and NSP12 of SARS-CoV-2 was studied by the method of molecular docking.

Results: The interaction energies and spatial configurations of dye molecules in complexes with NSP3, NSP5, and NSP12 have been determined.

Conclusion: A number of anionic dyes showing lower values of the total energy Etot could be recommended for practical research in the development of agents for the detection and inactivation of the coronavirus.

Keywords SARS-CoV-2      proteases      polymethine dyes      squarylium dyes      noncovalent interaction      molecular docking     
Corresponding Author(s): Pavel Pronkin   
Just Accepted Date: 09 August 2021   Online First Date: 15 September 2021    Issue Date: 01 December 2021
 Cite this article:   
Pavel Pronkin,Alexander Tatikolov. Molecular docking of cyanine and squarylium dyes with SARS-CoV-2 proteases NSP3, NSP5 and NSP12[J]. Quant. Biol., 2021, 9(4): 440-450.
 URL:  
https://academic.hep.com.cn/qb/EN/10.15302/J-QB-021-0263
https://academic.hep.com.cn/qb/EN/Y2021/V9/I4/440
Dye Run Aff. (kcal mol–1) Etot (kcal mol–1) EVdW (kcal mol–1) Eel (kcal mol–1)
NSP3 SQ1.1 18 –7.71 19.35 ± 1.82 –10.35 ± 5.89 –35.90 ± 5.74
SQ1.2 5 –7.79 23.20 ± 3.09 –9.35 ± 9.15 –43.81 ± 11.07
SQ1.3 5 –8.14 –57.7 ± 2.7 0.57 ± 9.9 –53.5 ± 11.2
SQ1.4 15 –7.04 43.56 ± 1.98 –1.30 ± 6.33 –53.09 ± 7.49
SQ1.5 23 –7.18 44.59 ± 0.86 –6.63 ± 5.65 –46.71 ± 5.94
SQ1.6 22 –7.25 4.80 ± 2.87 –5.73 ± 7.23 –49.20 ± 9.28
SQ1.7 3 –7.12 –59.85 ± 1.38 –7.76 ± 7.70 –43.93 ± 8.65
NSP5 SQ1.1 24 –9.01 26.10 ± 2.59 –21.67 ± 5.84 –19.69 ± 6.38
SQ1.2 7 –7.45 20.70 ± 2.28 –15.02 ± 2.17 –44.92 ± 4.10
SQ1.3 12 –7.83 –68.4 ± 1.24 –12.25 ± 5.3 –54.8 ± 5.3
SQ1.4 15 –8.41 38.06 ± 3.88 –22.83 ± 8.02 –46.24 ± 7.23
SQ1.5 8 –8.59 38.46 ± 5.75 –29.72 ± 5.28 –41.73 ± 13.48
SQ1.6 7 –8.632 –0.15 ± 6.69 –21.84 ± 6.86 –43.52 ± 12.02
SQ1.7 14 –8.06 –65.97 ± 1.98 –25.65 ± 6.53 –33.01 ± 5.89
NSP12 SQ1.1 3 –7.74 –36.66 ± 3.16 –13.27 ± 3.18 –50.59 ± 5.29
SQ1.2 24 –7.23 11.14 ± 1.19 –11.51 ± 5.34 –58.86 ± 5.96
SQ1.3 7 –7.08 –76.9 ± 1.2 –14.02 ± 3.8 –62.5 ± 4.2
SQ1.4 9 –6.67 23.36 ± 4.22 –15.68 ± 7.31 –62.55 ± 9.23
SQ1.5 22 –6.70 29.99 ± 1.62 –15.99 ± 8.13 –57.97 ± 8.13
SQ1.6 24 –7.05 –14.41 ± 1.84 –10.79 ± 5.42 –64.79 ± 5.22
SQ1.7 22 –8.08 –77.65 ± 4.53 –12.84 ± 5.77 –58.70 ± 2.47
Tab.1  Results of molecular docking of anionic squarylium dyes SQ1.1–SQ1.7 with proteases NSP3, NSP5, NSP12
Dye X NSP3 NSP5 NSP12
Run Aff. (kcal mol–1) Etot (kcal mol–1) Run Aff. (kcal mol–1) Etot (kcal mol–1) Run Aff. (kcal mol–1) Etot (kcal mol–1)
SQ1.1 S 16 –6.55 –45.4 ± 2.1 5 –7.71 –43.8 ± 1.13 20 –7.14 –47.6 ± 2.6
SQ1.2 22 –6.21 –15.8 ± 1.51 16 –7.98 –21.6±1.96 2 –7.42 –22.4 ±3.2
SQ1.3 22 –6.95 –33.9 ± 0.51 12 –8.06 –29.3 ± 0.71 22 –7.58 –41.1 ± 3.7
SQ1.4 1 –6.56 33.4± 1.14 14 –8.01 23.0± 1.03 3 –7.34 32.1± 0.69
SQ1.5 O 15 –6.82 –62.1 ± 2.3 11 –7.40 –69.2 ± 4.2 22 –7.21 –63.2 ± 2.7
SQ1.6 21 –6.71 –54.3 ± 3.3 18 –8.18 –60.3 ± 1.64 10 –7.55 –55.9 ± 2.9
SQ1.7 C(CH3)2 15 –7.26 –35.2 ± 1.76 12 –8.19 –35.2 ±1.76 4 –6.96 –39.9 ±0.97
SQ2.1 S 22 –7.02 –19.8 ±2.8 11 –8.46 –19.23 ± 2.7 18 –7.22 –24.2 ± 1.71
SQ2.2 6 –6.97 –24.5 ± 1.96 – – – – – –
SQ2.3 20 –8.06 17.25 ± 1.28 11 –9.50 –1.78±2.5 4 –8.50 15.5 ± 1.82
SQ2.4 19 –6.96 –5.16± 1.35 3 –9.31 –3.14±4.7 22 –7.58 –6.38± 2.4
SQ2.5 O 19 –6.76 –42.7 ±1.1 15 –7.60 –51.2 ± 3.2 24 –4.02 –41.9 ± 1.11
SQ2.6 16 –7.75 –39.1 ±1.5 21 –7.87 –47.9 ± 3.5 1 –7.58 –39.3 ± 0.98
SQ2.7 3 –6.49 58.4 ± 1.19 10 –7.99 46.48 ±1.82 10 –7.53 56.1 ± 0.87
SQ2.8 15 –6.84 –7.97±0.70 8 –9.82 –26.6 ± 2.5 20 –8.42 –7.48 ± 0.66
SQ2.9 13 –6.58 –59.2 ± 2.1 9 –9.12 –72.8 ± 2.0 21 –7.70 –59.3 ± 1.38
SQ2.10 C(CH3)2 8 –6.97 –26.7 ± 1.12 1 –8.22 –27.7 ± 3.0 23 –7.37 –32.0 ± 3.4
SQ2.11 S 11 –6.56 –22.8 ± 1.86 7 –7.41 –28.3 ± 1.45 21 –7.93 –31.3 ± 2.9
SQ2.12 O 8 –6.71 –109.0 ±0.85 19 –7.64 –124.2 ±3.6 1 –7.74 –120.1 ±0.82
SQ2.13 C(CH3)2 18 –6.96 –81.6 ± 1.4 22 –8.04 –83.3 ± 2.7 17 –7.60 –91.1 ±2.03
SQ3.1 S 21 –7.62 –35.5 ± 1.16 10 –7.24 –43.8 ± 2.4 2 –7.63 –38.2 ± 0.96
SQ3.2 8 –6.63 –39.3 ± 1.3 4 –8.08 –43.7 ± 2.9 1 –7.79 –43.8 ± 2.1
SQ3.3 O 1 –7.48 –46.2 ± 2.6 11 –9.16 –50.7 ± 1.43 19 –8.18 –42.6 ± 1.51
SQ3.4 17 –6.24 –57.2 ± 2.1 6 –8.64 –66.5 ± 2.6 6 –7.44 –59.1 ± 1.05
SQ3.5 7 –7.31 –60.8 ± 1.44 3 –7.60 –73.2 ± 1.04 22 –7.72 –66.6 ± 1.15
SQ3.6 C(CH3)2 15 –7.10 –19.01± 2.7 1 –8.21 –17.67±2.8 8 –7.31 –16.47±1.48
SQ4.1 S 23 –7.89 –4.64 ± 0.67 2 –8.68 –47.1 ± 2.4 13 –7.80 –39.1 ± 0.87
SQ4.2 9 –7.43 –25.9 ± 2.2 16 –8.76 –35.1 ± 2.7 15 –6.70 –29.4 ± 1.17
SQ4.3 24 –7.37 –18.8 ±1.09 5 –9.11 –28.7 ± 2.1 9 –7.76 –28.1 ± 3.4
SQ4.4 O 2 –6.53 –14.0 ± 1.76 7 –8.86 –14.64±0.98 4 –8.67 –18.41 ±1.47
SQ4.5 9 –7.24 –38.1 ±5.2 8 –8.12 –45.1 ± 2.2 19 –8.11 –37.6 ± 1.36
SQ4.7 4 –8.34 –39.8 ± 2.3 16 –8.31 –47.5 ± 2.0 1 –7.76 –46.2 ± 1.46
SQ4.6 15 –7.33 –46.9 ± 1.81 7 –8.03 –51.4 ± 1.38 22 –7.64 –45.5 ± 0.62
SQ4.8 C(CH3)2 18 –7.89 21.5 ± 2.5 6 –10.5 25.0 ± 2.64 9 –7.97 17.01 ±3.2
Tab.2  Results of molecular docking of anionic cyanine dyes with proteases NSP3, NSP5, NSP12
Fig.1  Structural formulas of cationic carbocyanines, as well as neutral and anionic squarylium dyes.
Fig.2  Result of docking of dyes SQ1.3 with NSP5 (A) and SQ1.7 with NSP12 (B), initial configurations of dyes: SQ1.3 (C), SQ1.7 (D).
Fig.3  Structural formulas of the studied anionic cyanine dyes.
Fig.4  Results of docking of anionic dyes with SARS-CoV-2 proteases.
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