In Silico and In Vitro Studies of Alchemilla viridiflora Rothm—Polyphenols’ Potential for Inhibition of SARS-CoV-2 Internalization
Abstract
:1. Introduction
2. Results and Discussion
2.1. LC-MS Chemical Analysis (Phytochemical Analysis)
2.2. Molecular Docking Studies
2.3. In Vitro SARS-CoV-2 Internalization Inhibition Assays
3. Materials and Methods
3.1. Plant Material and Extract Preparation
3.2. Chemicals
3.3. LC-MS Chemical Analysis
3.4. Molecular Docking Simulations
3.4.1. Dataset
3.4.2. Docking Parameters
3.5. Molecular Dynamics (MD) Simulation
3.6. In Vitro SARS-CoV-2 Internalization Inhibition Assays
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Compound | Formula: | Molecular Weight: | Match Score: | RT: | Adduct/Loss: |
---|---|---|---|---|---|
Pedunculagin | C34H24O22 | 784.076 | 0.998 | 9.35 | −/H+ |
Galloyl-HHDP hexose | C27H22O17 | 618.086 | 0.999 | 12.41 | Na+/− |
Isoquercitrin | C21H20O12 | 464.095 | 0.999 | 12.44 | H+/− |
Quercetin 3-(6″-ferulylglucoside) | C31H28O15 | 640.143 | 0.993 | 12.46 | −/H+ |
Tellimagrandin I | C34H26O22 | 786.092 | 0.993 | 16.4 | −/H+ |
Brevifolin carboxylic acid | C13H8O8 | 292.022 | 0.997 | 21.5 | −/H2OH+ |
Myricetin 3-O-glucuronide | C21H18O14 | 494.07 | 0.973 | 22.9 | CH3OHH+/− |
Tellimagrandin II | C41H30O26 | 938.103 | 0.992 | 23.97 | −/H+ |
Pentagalloylglucose | C41H32O26 | 940.118 | 0.879 | 29.36 | −/H+ |
Kaempferol 7-O-glucuronide | C21H18O12 | 462.08 | 0.996 | 30.97 | Na+/− |
HHDP-hexoside | C20H18O14 | 482.07 | 0.961 | 31.1 | CH3OHH+/− |
Quercetin 3-methyl ether 7-glucuronide | C22H20O13 | 492.09 | 0.985 | 31.13 | −/H+ |
Kaempferol 7-O-glucoside | C21H20O11 | 448.101 | 0.981 | 33.06 | Na+/− |
Di-O-methylquercetin | C17H14O7 | 330.074 | 0.999 | 33.82 | −/H+ |
Tiliroside | C30H26O13 | 594.137 | 0.996 | 37.7 | −/H+ |
Isorhamnetin-3-O-glucoside | C22H22O12 | 478.111 | 0.963 | 39.37 | NH4+/− |
Miquelianin | C21H18O13 | 478.075 | 0.96 | 39.37 | NH4+/− |
Compound | Bind Energy [kcal/mol] | Interacting Residues * |
---|---|---|
Quercetin 3-(6″-ferulylglucoside) | −8.035 | Gln160, Glu151 (1.63 Å), Phe157 (2.63 Å), Ser161 (1.84 Å), Tyr 162 (2.83 Å) |
Tellimagrandin I | −8.022 | Gln160 (2.82 Å), Glu151 (1.57 Å, 1.71 Å), Phe157 (2.82 Å, 2.84 Å) |
Tellimagrandin II | −7.955 | Gln160, Glu151 (1.59 Å, 1.64 Å), Gly163 (3.10 Å), Tyr116, Tyr116 (1.73 Å, 1.94 Å), Tyr162 (2.24 Å) |
Pedunculagin | −7.848 | Gln160 (2.23 Å), Glu151 (1.64 Å, 2.15 Å), Gly163 (2.70 Å), Leu119, Phe157, Tyr116 (1.69 Å), Tyr162 (2.46 Å) |
Isorhamnetin-3-O-glucoside | −7.761 | Glu151 (1.63 Å, 1.76 Å), Leu119, Leu159 (1.60 Å), Phe157, Ser161 (2.92 Å), Tyr162 (2.79 Å) |
Tiliroside | −7.633 | Arg70, Gln73 (1.50 Å), Gln160, Glu151 (1.61 Å), Lys84 (2.73 Å), Phe157 (2.42 Å), Tyr120 |
Pentagalloylglucose | −7.601 | Gln160 (2.52 Å), Gln160, Glu151 (1.54 Å, 1.62 Å), Ser161 (2.64 Å), Tyr156, Tyr162 (2.02 Å) |
Kaempferol 7-O-glucuronide | −7.519 | Glu151 (1.92 Å), Phe157 (2.43 Å), Tyr120 (1.20 Å) |
Di-O-methylquercetin | −7.515 | Gln160 (2.38 Å), Glu151 (1.59 Å, 1.60 Å), Phe123, Phe157 (2.33 Å), Tyr156 |
HHDP-hexoside | −7.506 | Glu151 (1.71 Å, 2.00 Å), Phe157, Ser161 (2.39 Å), Tyr116 (2.34 Å) |
Miquelianin | −7.406 | Gln160 (3.09 Å), Glu151 (1.72 Å, 1.92 Å), Leu119, Phe157, Ser161 (1.49 Å) |
Myricetin 3-O-glucuronide | −7.404 | Glu151 (1.67 Å, 1.94 Å), Leu119, Leu159 (1.73 Å), Phe157, Ser161 (1.46 Å) |
Umifenovir ** | −7.384 | Glu151 (1.65 Å), Ser161 (1.96 Å), Tyr116 |
Quercetin ** | −7.189 | Gln160 (2.07 Å), Glu151 (1.63 Å, 1.78 Å), Phe123, Phe157 (2.02 Å), Tyr156 |
Kaempferol 7-O-glucoside | −7.121 | Gln160 (2.48 Å, 3.02 Å), Glu151 (1.66 Å, 1.70 Å), Phe157 (1.97 Å), Tyr162 (1.90 Å) |
Galloyl-HHDP hexose | −6.964 | Gln160 (2.56 Å, 2.77 Å), Glu151 (1.56 Å, 1.82 Å), Leu159 (1.70 Å, 1.96 Å) |
Isoquercitrin | −6.953 | Gln160 (3.03 Å), Glu151 (1.63 Å, 1.64 Å), Leu159 (1.89 Å), Ser161 (1.80 Å, 2.32 Å) |
Quercetin 3-methyl ether 7-glucuronide | −6.579 | Glu151 (1.58 Å, 1.62 Å), Lys84 (3.06 Å), Lys84, Tyr120 (1.62 Å) |
Brevifolin carboxylic acid | −6.359 | Arg70 (1.53 Å), Tyr162 (1.84 Å), Tyr172 (1.63 Å) |
Compound | The Most Favorable Binding Pose ** | Bind Energy [kcal/mol] | Interacting Residues * |
---|---|---|---|
Pentagalloylglucose | −7.685 | Asp320 (2.29 Å, 2.50 Å), Lys351 (2.29, 2.32 Å), Lys351, Lys352 (2.04 Å), Pro317 (2.50 Å), Thr413 (2.61 Å, 2.68 Å), Tyr297, Tyr353 (2.41 Å, 2.71 Å) | |
Quercetin methyl ether glucuronide | −7.667 | Asp320 (2.72 Å), Glu348 (2.09 Å), Lys351 (2.07 Å), Thr413, Thr413 (3.01 Å), Trp301 (2.00 Å), Trp411,Tyr297, Tyr353 (2.51 Å) | |
Tiliroside | −7.594 | Asp320, Glu348 (2.15 Å), Lys351 (2.05 Å), Thr413, Tyr297, Tyr353 (2.82 Å) | |
Kaempferol 7-O-glucuronide | −7.452 | Asn300 (1.82 Å), Asp320, Lys351 (2.05 Å), Trp301 (2.36 Å), Tyr297 | |
Kaempferol 7-O-glucoside | −7.264 | Asn300 (1.85 Å), Asp320, Lys351 (2.02 Å), Trp301 (2.30 Å), Tyr297 | |
Quercetin | −7.205 | Asn300 (2.60 Å), Asp320, Lys351 (1.94 Å, 2.85 Å), Thr349 (2.72 Å), Trp301 (2.28 Å), Tyr297 (2.51 Å), Tyr353 | |
Miquelianin | −6.986 | Asp320 (2.44 Å), Glu348 (2.65 Å), Lys351 (1.98 Å), Thr349 (2.60 Å), Thr413 | |
Brevifolin carboxylic acid *** | −6.976 | Lys351 (2.00 Å), Thr316, Trp301 (2.32 Å), Trp301, Tyr297 | |
Quercetin 3-(6″-ferulylglucoside) | −6.875 | Arg418 (2.65 Å), Arg418, Asn309 (2.90 Å), Asn313 (2.37 Å),Glu312, Ile345, Lys350 (2,84 Å), Ser346 (2.83 Å), Thr388 | |
Pedunculagin | −6.855 | Asn300 (2.78 Å), Asp320, Ser298, Tyr297 (2.33 Å, 2.49 Å) | |
Myricetin 3-O-glucuronide | −6.802 | Asp320, Gly318 (2.17 Å), Lys351 (1.99 Å), Thr349 (2.72 Å),Thr413, Tyr297 | |
Isoquercitrin | −6.799 | Asp320, Gly318 (2.52 Å), Lys351 (2.03 Å, 2.52 Å), Ser346 (3.02 Å), Thr413, Tyr297 | |
Tellimagrandin I | −6.76 | Asp320, Glu319 (2.77 Å), Gly318, Ser321, Thr413 (1.93 Å), Tyr297 | |
Di-O-methylquercetin | −6.713 | Asn300 (2.05 Å), Glu348, Tyr297, Tyr301, Tyr353 | |
Isorhamnetin-3-O-glucoside | −6.467 | Asp320, Asp320 (2.71 Å), Gly318, Lys351 (2.25 Å, 2.40 Å), Ser346 (2.65 Å), Thr413, Thr413 (2.56 Å), Tyr297 | |
Galloyl-HHDP-hexose | −6.365 | Asp320, Asp320 (2.07 Å, 2.92 Å), Thr413, Trp301, Trp411 (2.51 Å), Tyr297, Tyr353 (2.67 Å) | |
Tellimagrandin II | −6.051 | Arg323, Asp320 (2.76 Å), Tyr297 | |
HHDP-hexoside | −5.897 | Lys351 (2.02 Å), Thr413 (2.46 Å), Tyr353 |
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Suručić, R.; Radović Selgrad, J.; Kundaković-Vasović, T.; Lazović, B.; Travar, M.; Suručić, L.; Škrbić, R. In Silico and In Vitro Studies of Alchemilla viridiflora Rothm—Polyphenols’ Potential for Inhibition of SARS-CoV-2 Internalization. Molecules 2022, 27, 5174. https://doi.org/10.3390/molecules27165174
Suručić R, Radović Selgrad J, Kundaković-Vasović T, Lazović B, Travar M, Suručić L, Škrbić R. In Silico and In Vitro Studies of Alchemilla viridiflora Rothm—Polyphenols’ Potential for Inhibition of SARS-CoV-2 Internalization. Molecules. 2022; 27(16):5174. https://doi.org/10.3390/molecules27165174
Chicago/Turabian StyleSuručić, Relja, Jelena Radović Selgrad, Tatjana Kundaković-Vasović, Biljana Lazović, Maja Travar, Ljiljana Suručić, and Ranko Škrbić. 2022. "In Silico and In Vitro Studies of Alchemilla viridiflora Rothm—Polyphenols’ Potential for Inhibition of SARS-CoV-2 Internalization" Molecules 27, no. 16: 5174. https://doi.org/10.3390/molecules27165174