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Research Article
Computational screening approaches for investigating potential activity of phytoligands against SARS-CoV-2
Rakesh Kumar Sharma
Saveetha Institute of Medical and Technical Sciences
Corresponding Author
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Objective: SARS-CoV-2 causes COVID-19, a life-threatening respiratory illness with high rates of morbidity and mortality. As on date, there is no specific medicine to prevent or treat COVID-19. Therefore, there is an acute need to identify evidence-based holistic and safe mitigators.
Methods: The present study is aimed to screen ligands of herbal origin using rationale based bioprospection analysis and subsequently predict their binding potential subdue the major drug targets for novel Coronavirus by employing computer-aided virtual screening. Further, comparative analysis of the binding potential of an approved chemical analogue and selected herbal ligands were also predicted. The selection of receptors was performed based on their pathophysiological relevance, as assessed by a PubMed based keyword hits matrix analysis. The drug likeliness and ADMETox descriptors of 24 herbal ligands were computationally predicted. Docking studies were further conducted with those phytoligands that qualified these parameters. An existing antimalarial drug, hydroxychloroquine, was also docked with all the selected viral receptors and its theoretical binding energy was set up as a standard for comparison as well as scrutinization of binding energies of the phytoligands.
Results: The docking studies suggested that the herbal ligand, namely, gamma-glutamyl-S-allylcysteine demonstrated highly significant binding energies with viral spike glycoprotein, endoribonuclease and main protease (binding energy ≥ -490 kcal/mol for all the tested viral receptors).
Conclusion: Gamma-glutamyl-S-allylcysteine demonstrated more significant binding potential as compared to the known chemical analogue, i.e., hydroxychloroquine, as observed in the computational docking studies. This study serves to present pre-eminent information for further clinical studies highlighting the utility of herbal ligands as probable lead molecules for mitigating novel Coronavirus infection.
Keywords
Corona virus, COVID-19, Drug designing, Herbal drug, Molecular docking, SARS-CoV-2
Figure 1
Figure 2
Figure 3
Table 1. Selection of COVID-19 virulence factors on the basis of relevance score as assessed by keyword hits scoring matrix
|
Parameter |
Rationale of selection |
Total No. of Hits (N) |
Hits Screened (n) |
Relevant Hits (r) |
Percentage Relevance† |
Relevance Score§ |
|
Viral Spike Glycoprotein inhibitor |
Enveloped viruses enter cells by viral glycoprotein-mediated binding (Viral spikes – S proteins) to host cells and subsequent fusion of virus and host cell membranes (Liu et al., 2020). |
20 |
20 |
18 |
90 |
1 |
|
Viral Endoribonuclease inhibitor |
Endoribonuclease catalyses the processing and degradation of both cellular and viral RNAs, thus determining the amount and functionality of specific RNA molecules in a cell at any given time. It degrades the host mRNA, while cleaves the precursor viral RNAs to produce active genetic material (Balkrishna et al., 2020). |
103 |
20 |
13 |
65 |
0.58 |
|
Viral Protease inhibitor |
Viral proteases are enzymes encoded by the genetic material of viral pathogens so as to catalyse the cleavage of specific peptide bonds in viral polyprotein precursors or in cellular proteins. The protease cleaves the precursor viral polyprotein to produce functional proteins and enzymes (Jo et al., 2020). |
1516 |
20 |
12 |
60 |
0.5 |
|
Anti-bronchitis Herb |
Coronavirus causes respiratory illnesses. Hence, herbs providing symptomatic relief against respiratory symptoms might prove to be beneficial (Carlos et al., 2020). |
551 |
20 |
9 |
45 |
0.25 |
|
Anti-gastroenteritis Herb |
Coronavirus also causes gastroenteritis. Thus, herbs providing symptomatic relief against gastrointestinal ailments might prove to be beneficial (Chen et al., 2020). |
52 |
20 |
8 |
40 |
0.16 |
|
Interferon regulatory herb |
Interferons (IFNs) are cytokines which are used for communication between cells to trigger the protective defense of the immune system that help eradicate pathogens, Coronavirus in this case (Balkrishna et al., 2020). |
952 |
20 |
6 |
30 |
0 |
Due to technical limitations, table 2 is only available as a download in the supplemental files section.
Table 3. Selected Herbal moieties showing probable antiviral utility as assessed by employing extensive literature surge.
|
Plant Source§ |
Predominant phytocompound |
Activity explored† |
Binary Score |
Weightage Score |
Fuzzy Score* |
Probable antiviral utility |
Ref |
||
|
S2 |
NSP 15 |
3CL pro |
|||||||
|
Alisma canaliculatum A.Braun & C.D.Bouché |
Alisol A 24-Acetate |
+ |
− |
− |
2 |
1.16 |
0.46 |
Anti-influenza activity observed as the herbal moiety inactivates the hemagglutinin spike receptor. |
1 |
|
Allium cepa L. |
Allicin |
+ |
+ |
+ |
3 |
1.66 |
0.66 |
Hinders virus attachment to host cell, alter transcription and translation of viral genome in host cell and also affect viral assembly. |
2 |
|
Allium sativum L. |
Gamma-Glutamyl-S-allylcysteine |
+ |
+ |
+ |
6 |
2.49 |
1 |
Acts as protease inhibitor mainly. |
3 |
|
Artemisia capillaris Thunb. |
Beta-caryophyllene |
+ |
− |
+ |
5 |
1.91 |
0.76 |
Symptomatic alleviation in case of hepatitis virus infection. |
4 |
|
Artemisia caruifolia Buch. -Ham. ex Roxb. |
Caruilignan |
+ |
− |
+ |
3 |
1.25 |
0.5 |
Anti-influenza and anti-herpes simplex virus activity; also inhibits HIV-1 protease. |
5, 6 |
|
Asparagus racemosus Willd. |
Isoasparagine |
− |
− |
− |
3 |
0.40 |
0.3 |
Symptomatic alleviation in case of herpes virus infection. |
7 |
|
Berberis aristata DC. |
Berberine |
+ |
− |
+ |
5 |
1.91 |
0.76 |
Inhibits enterovirus 71 entry and replication by downregulating the MEK/ERK signaling pathway and autophagy. |
8 |
|
Boswellia serrata Roxb. |
11-keto-beta-boswellic acid |
+ |
− |
+ |
3 |
1.66 |
0.66 |
Inhibits Chikungunya and Vesicular stomatitis virus infections by blocking their entry. |
9 |
|
Camellia sinensis (L.) Kuntze |
Quercetin |
+ |
− |
+ |
5 |
1.91 |
0.76 |
Suppressed Hepatitis C virus entry, and also inhibited viral RNA replication. |
10 |
|
Chlorophytum borivilianum Santapau & R.R. Fern. |
Neotigogenin |
− |
− |
− |
2 |
0.40 |
0.3 |
Cytokine modulating potential. |
11 |
|
Curcuma longa L. |
Curcumin |
+ |
− |
+ |
5 |
1.91 |
0.76 |
Inhibits entry of Chikungunya and Vesicular stomatitis virus. |
9 |
|
Epimedium flavum Stearn |
Wushanicariin |
+ |
− |
− |
1 |
1 |
0.4 |
Induced the secretion of type I IFN and pro-inflammatory cytokines. |
12 |
|
Gingko biloba L. |
Amentoflavone |
+ |
− |
+ |
4 |
1.66 |
0.66 |
Inhibits viral protease, specifically in case of HIV infection. |
13 |
|
Houttuynia cordata Thunb. |
β-myrcene |
+ |
− |
+ |
5 |
1.91 |
0.76 |
Inactivation of 3C-like proteinase of murine Coronavirus and dengue virus. |
14 |
|
Melissa officinalis L. |
Citronellal |
+ |
+ |
− |
5 |
1.49 |
0.59 |
Inhibition of HIV-1 protease. |
15 |
|
Ocimum tenuiflorum L. |
Carvacrol |
− |
− |
+ |
3 |
0.75 |
0.35 |
Inactivation of viral protease in case of HIV infection. |
16 |
|
Paeonia lactiflora Pall. |
Paeoniflorin |
+ |
− |
− |
3 |
1.41 |
0.56 |
Inhibits viral entry in case of Influenza virus infection. |
17 |
|
Phyllanthus amarus Schumach. & Thonn. |
Gallotannin |
− |
+ |
+ |
5 |
1.49 |
0.59 |
Halts the process of viral replication in case of Herpes simplex virus infection. |
18 |
|
Rheum rhabarbarum L. |
Malic acid |
+ |
− |
+ |
4 |
1.91 |
0.76 |
Inhibits viral entry by ceasing the endosomal fusion in case of influenza virus. |
19 |
|
Salvia miltiorrhiza Bunge |
Salvianolic acid |
− |
+ |
+ |
5 |
1.49 |
0.59 |
Inhibition of HIV-1 integrase and protease. |
20 |
|
Taxillus sutchuenensis var. duclouxii (Lecomte) H.S.Kiu |
Butenolide |
+ |
− |
+ |
2 |
1.5 |
0.60 |
Inhibition of Hepatitis C viral NS3 serine protease and ceasing viral entry. |
21 |
|
Tinospora cordifolia (Willd.) Hook.f. & Thomson |
Tinosporaside |
+ |
+ |
+ |
5 |
2.49 |
1 |
Immunomodulatory activity; Anti-HIV activity wherein it acts as viral ribonuclease inhibitor. |
22 |
|
Withania somnifera (L.) Dunal |
Withanolide |
+ |
+ |
+ |
3 |
1.41 |
0.56 |
Disrupts interactions between viral S-protein receptor binding domain and Host ACE2 receptor. |
23 |
|
Zingiber officinale Roscoe |
6-Gingerol |
− |
+ |
+ |
5 |
1.49 |
0.59 |
Inhibits Hepatitis C virus protease. |
24 |
§Plants are selected on the basis of extensive literature surge, specifically focusing on their ethno-medicinal attributes, symptomatic relief provision abilities and direct/indirect antiviral activity, if any.
†Symbols of + and – denote the presence and absence of viral virulence factor inhibitory properties in the given plant, as deduced on the basis of keyword search matrix analysis using PubMed search engine.
*Fuzzy score μS= (S-minS)/ (maxS-minS), wherein shaded cells represent the ligands selected for further study with a fuzzy score > 0.5.
Table 4. Physicochemical properties of phytoligands in comparison with the standard chemotherapeutic agent.
|
Ligand/ Standard |
Physicochemical Properties |
||||
|
Mol. Wt. (≤ 500 D) |
Log P (≤ 5)† |
H-Bond Donor (≤ 5) |
H-Donor Acceptor (≤ 10) |
Lipinski violations (if any)* |
|
|
Allicin |
162.02 |
0.237 |
0 |
1 |
0 |
|
Amentoflavone |
538.09 |
2.030 |
6 |
10 |
1 |
|
Berberine |
336.12 |
2.473 |
0 |
4 |
0 |
|
Beta-caryophyllene |
204.19 |
6.044 |
0 |
0 |
1 |
|
11-keto-beta-boswellic acid |
470.34 |
8.131 |
2 |
4 |
1 |
|
Butenolide |
84.02 |
0.308 |
0 |
2 |
0 |
|
Citronellal |
154.14 |
3.591 |
0 |
1 |
0 |
|
Curcumin |
368.13 |
1.945 |
2 |
6 |
0 |
|
Gallotannin |
1700 |
9.537 |
25 |
46 |
4 |
|
Gamma-Glutamyl-S-allylcysteine |
290.09 |
-2.68 |
4 |
7 |
0 |
|
6-Gingerol |
294.18 |
2.437 |
2 |
4 |
0 |
|
Malic acid |
134.02 |
-1.474 |
3 |
5 |
0 |
|
β-myrcene |
136.13 |
4.170 |
0 |
0 |
0 |
|
Paeoniflorin |
480.16 |
-0.464 |
5 |
11 |
1 |
|
Quercetin |
302.04 |
1.834 |
5 |
7 |
0 |
|
Salvianolic acid |
494.12 |
2.898 |
7 |
10 |
1 |
|
Tinosporaside |
492.20 |
0.54 |
4 |
10 |
0 |
|
Withanolide |
470.27 |
3.263 |
2 |
6 |
0 |
|
Hydroxychloroquine |
335.88 |
4.00 |
4 |
2 |
0 |
†Logarithm of compound partition coefficient between n-octanol and water.
*Shaded cell indicates phytoligand with more than 1 Lipinski violations and hence is eliminated at this stage itself.
Table 5. ADMETox values of phytoligands in comparison with the standard chemotherapeutic agent.
|
Ligand/ Standard |
Absorption |
Distribution |
Metabolism |
Excretion |
Toxicity |
|||
|
Caco-2 permeability (value ≥ 0.5) |
Human intestinal absorption (value ≥ 0.5) |
Plasma Protein binding (value ≥ 0.5) |
Water solubility (logS ≥ - 4) |
P-glyco-protein activator (value ≥ 0.5) |
CYP3A4 inhibition (value ≥ 0.5) |
Acute oral toxicity (Kg/mol) (value ≥ 1.0) |
Ames test (value ≥ 0.5) |
|
|
Allicin |
0.58 (+) |
0.91 (+) |
0.50 (+) |
-0.89 (+) |
0.98 (+) |
0.92 (-) |
1.935 (-) |
0.61 (-) |
|
Amentoflavone |
0.87 (+) |
0.98 (+) |
1.11 (+) |
-3.36 (+) |
0.44 (-) |
0.61 (-) |
1.822 (-) |
0.68 (-) |
|
Berberine |
0.94 (+) |
0.77 (+) |
0.83 (+) |
-2.97 (+) |
0.68 (+) |
0.58 (-) |
1.545 (-) |
0.75 (-) |
|
Beta-caryophyllene |
0.86 (+) |
0.98 (+) |
0.83 (+) |
-4.68 (+) |
0.89 (+) |
0.86 (-) |
2.366 (-) |
0.99 (-) |
|
11-keto-beta-boswellic acid |
0.54 (+) |
0.99 (+) |
1.05 (+) |
-3.45 (+) |
0.63 (+) |
0.79 (-) |
2.834 (-) |
0.82 (-) |
|
Butenolide |
0.76 (+) |
0.96 (+) |
0.096 (-) |
0.23 (+) |
0.98 (+) |
0.98 (-) |
1.976 (-) |
0.77 (-) |
|
Citronellal |
0.92 (+) |
0.97 (+) |
0.70 (+) |
-2.44 (+) |
0.98 (+) |
0.96 (-) |
2.307 (-) |
0.99 (-) |
|
Curcumin |
0.76 (+) |
0.97 (+) |
0.83 (+) |
-3.36 (+) |
0.59 (+) |
0.53 (-) |
1.992 (-) |
0.96 (-) |
|
Gamma-Glutamyl-S-allylcysteine |
0.92 (+) |
0.63 (+) |
0.50 (+) |
-1.68 (+) |
0.93 (+) |
0.74 (-) |
1.648 (-) |
0.55 (-) |
|
6-Gingerol |
0.59 (+) |
0.99 (+) |
0.85 (+) |
-3.23 (+) |
0.89 (+) |
0.59 (-) |
2.290 (-) |
0.57 (-) |
|
Malic acid |
0.95 (+) |
0.77 (+) |
0.23 (-) |
0.27 (+) |
0.98 (+) |
0.90 (-) |
0.844 (+) |
0.87 (-) |
|
β-myrcene |
0.77 (+) |
0.96 (+) |
0.43 (-) |
-3.44 (+) |
0.98 (+) |
0.66 (-) |
1.660 (-) |
0.92 (-) |
|
Paeoniflorin |
0.82 (+) |
0.41 (-) |
0.67 (+) |
-2.97 (+) |
0.65 (+) |
0.85 (-) |
3.502 (-) |
0.53 (-) |
|
Quercetin |
0.64 (+) |
0.98 (+) |
1.17 (+) |
-2.99 (+) |
0.91 (+) |
0.69 (-) |
2.559 (-) |
0.90 (-) |
|
Salvianolic acid |
0.93 (+) |
0.96 (+) |
1.03 (+) |
-3.20 (+) |
0.65 (+) |
0.83 (-) |
2.069 (-) |
0.58 (-) |
|
Tinosporaside |
0.84 (+) |
0.83 (+) |
0.50 (+) |
-3.65 (+) |
0.54 (+) |
0.75 (-) |
3.236 (-) |
0.70 (-) |
|
Withanolide |
0.62 (+) |
0.97 (+) |
1.18 (+) |
-4.00 (+) |
0.51 (+) |
0.85 (-) |
3.660 (-) |
0.78 (-) |
|
Hydroxy-chloroquine |
0.66 (+) |
0.99 (+) |
0.86 (+) |
-4.00 (+) |
0.84 (+) |
0.83 (-) |
2.684 (-) |
0.70 (-) |
*Denoted ‘+’ or ‘-’ sign relates to the presence or absence of a predicted activity, respectively. Shaded cells indicate the descriptors violating the standard values, thereby excluding the respective phytoligand(s) from further studies.
Due to technical limitations, table 6 is only available as a download in the supplemental files section.
This is a list of supplementary files associated with this preprint. Click to download.
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Research Article
Computational screening approaches for investigating potential activity of phytoligands against SARS-CoV-2
Rakesh Kumar Sharma
Saveetha Institute of Medical and Technical Sciences
Corresponding Author
Badges
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This manuscript passed our Prescreen assessment
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CURRENT STATUS: Posted
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License:
This work is licensed under a CC BY 4.0 License. Read Full License
Objective: SARS-CoV-2 causes COVID-19, a life-threatening respiratory illness with high rates of morbidity and mortality. As on date, there is no specific medicine to prevent or treat COVID-19. Therefore, there is an acute need to identify evidence-based holistic and safe mitigators.
Methods: The present study is aimed to screen ligands of herbal origin using rationale based bioprospection analysis and subsequently predict their binding potential subdue the major drug targets for novel Coronavirus by employing computer-aided virtual screening. Further, comparative analysis of the binding potential of an approved chemical analogue and selected herbal ligands were also predicted. The selection of receptors was performed based on their pathophysiological relevance, as assessed by a PubMed based keyword hits matrix analysis. The drug likeliness and ADMETox descriptors of 24 herbal ligands were computationally predicted. Docking studies were further conducted with those phytoligands that qualified these parameters. An existing antimalarial drug, hydroxychloroquine, was also docked with all the selected viral receptors and its theoretical binding energy was set up as a standard for comparison as well as scrutinization of binding energies of the phytoligands.
Results: The docking studies suggested that the herbal ligand, namely, gamma-glutamyl-S-allylcysteine demonstrated highly significant binding energies with viral spike glycoprotein, endoribonuclease and main protease (binding energy ≥ -490 kcal/mol for all the tested viral receptors).
Conclusion: Gamma-glutamyl-S-allylcysteine demonstrated more significant binding potential as compared to the known chemical analogue, i.e., hydroxychloroquine, as observed in the computational docking studies. This study serves to present pre-eminent information for further clinical studies highlighting the utility of herbal ligands as probable lead molecules for mitigating novel Coronavirus infection.
Figure 1
Figure 2
Figure 3
Table 1. Selection of COVID-19 virulence factors on the basis of relevance score as assessed by keyword hits scoring matrix
|
Parameter |
Rationale of selection |
Total No. of Hits (N) |
Hits Screened (n) |
Relevant Hits (r) |
Percentage Relevance† |
Relevance Score§ |
|
Viral Spike Glycoprotein inhibitor |
Enveloped viruses enter cells by viral glycoprotein-mediated binding (Viral spikes – S proteins) to host cells and subsequent fusion of virus and host cell membranes (Liu et al., 2020). |
20 |
20 |
18 |
90 |
1 |
|
Viral Endoribonuclease inhibitor |
Endoribonuclease catalyses the processing and degradation of both cellular and viral RNAs, thus determining the amount and functionality of specific RNA molecules in a cell at any given time. It degrades the host mRNA, while cleaves the precursor viral RNAs to produce active genetic material (Balkrishna et al., 2020). |
103 |
20 |
13 |
65 |
0.58 |
|
Viral Protease inhibitor |
Viral proteases are enzymes encoded by the genetic material of viral pathogens so as to catalyse the cleavage of specific peptide bonds in viral polyprotein precursors or in cellular proteins. The protease cleaves the precursor viral polyprotein to produce functional proteins and enzymes (Jo et al., 2020). |
1516 |
20 |
12 |
60 |
0.5 |
|
Anti-bronchitis Herb |
Coronavirus causes respiratory illnesses. Hence, herbs providing symptomatic relief against respiratory symptoms might prove to be beneficial (Carlos et al., 2020). |
551 |
20 |
9 |
45 |
0.25 |
|
Anti-gastroenteritis Herb |
Coronavirus also causes gastroenteritis. Thus, herbs providing symptomatic relief against gastrointestinal ailments might prove to be beneficial (Chen et al., 2020). |
52 |
20 |
8 |
40 |
0.16 |
|
Interferon regulatory herb |
Interferons (IFNs) are cytokines which are used for communication between cells to trigger the protective defense of the immune system that help eradicate pathogens, Coronavirus in this case (Balkrishna et al., 2020). |
952 |
20 |
6 |
30 |
0 |
Due to technical limitations, table 2 is only available as a download in the supplemental files section.
Table 3. Selected Herbal moieties showing probable antiviral utility as assessed by employing extensive literature surge.
|
Plant Source§ |
Predominant phytocompound |
Activity explored† |
Binary Score |
Weightage Score |
Fuzzy Score* |
Probable antiviral utility |
Ref |
||
|
S2 |
NSP 15 |
3CL pro |
|||||||
|
Alisma canaliculatum A.Braun & C.D.Bouché |
Alisol A 24-Acetate |
+ |
− |
− |
2 |
1.16 |
0.46 |
Anti-influenza activity observed as the herbal moiety inactivates the hemagglutinin spike receptor. |
1 |
|
Allium cepa L. |
Allicin |
+ |
+ |
+ |
3 |
1.66 |
0.66 |
Hinders virus attachment to host cell, alter transcription and translation of viral genome in host cell and also affect viral assembly. |
2 |
|
Allium sativum L. |
Gamma-Glutamyl-S-allylcysteine |
+ |
+ |
+ |
6 |
2.49 |
1 |
Acts as protease inhibitor mainly. |
3 |
|
Artemisia capillaris Thunb. |
Beta-caryophyllene |
+ |
− |
+ |
5 |
1.91 |
0.76 |
Symptomatic alleviation in case of hepatitis virus infection. |
4 |
|
Artemisia caruifolia Buch. -Ham. ex Roxb. |
Caruilignan |
+ |
− |
+ |
3 |
1.25 |
0.5 |
Anti-influenza and anti-herpes simplex virus activity; also inhibits HIV-1 protease. |
5, 6 |
|
Asparagus racemosus Willd. |
Isoasparagine |
− |
− |
− |
3 |
0.40 |
0.3 |
Symptomatic alleviation in case of herpes virus infection. |
7 |
|
Berberis aristata DC. |
Berberine |
+ |
− |
+ |
5 |
1.91 |
0.76 |
Inhibits enterovirus 71 entry and replication by downregulating the MEK/ERK signaling pathway and autophagy. |
8 |
|
Boswellia serrata Roxb. |
11-keto-beta-boswellic acid |
+ |
− |
+ |
3 |
1.66 |
0.66 |
Inhibits Chikungunya and Vesicular stomatitis virus infections by blocking their entry. |
9 |
|
Camellia sinensis (L.) Kuntze |
Quercetin |
+ |
− |
+ |
5 |
1.91 |
0.76 |
Suppressed Hepatitis C virus entry, and also inhibited viral RNA replication. |
10 |
|
Chlorophytum borivilianum Santapau & R.R. Fern. |
Neotigogenin |
− |
− |
− |
2 |
0.40 |
0.3 |
Cytokine modulating potential. |
11 |
|
Curcuma longa L. |
Curcumin |
+ |
− |
+ |
5 |
1.91 |
0.76 |
Inhibits entry of Chikungunya and Vesicular stomatitis virus. |
9 |
|
Epimedium flavum Stearn |
Wushanicariin |
+ |
− |
− |
1 |
1 |
0.4 |
Induced the secretion of type I IFN and pro-inflammatory cytokines. |
12 |
|
Gingko biloba L. |
Amentoflavone |
+ |
− |
+ |
4 |
1.66 |
0.66 |
Inhibits viral protease, specifically in case of HIV infection. |
13 |
|
Houttuynia cordata Thunb. |
β-myrcene |
+ |
− |
+ |
5 |
1.91 |
0.76 |
Inactivation of 3C-like proteinase of murine Coronavirus and dengue virus. |
14 |
|
Melissa officinalis L. |
Citronellal |
+ |
+ |
− |
5 |
1.49 |
0.59 |
Inhibition of HIV-1 protease. |
15 |
|
Ocimum tenuiflorum L. |
Carvacrol |
− |
− |
+ |
3 |
0.75 |
0.35 |
Inactivation of viral protease in case of HIV infection. |
16 |
|
Paeonia lactiflora Pall. |
Paeoniflorin |
+ |
− |
− |
3 |
1.41 |
0.56 |
Inhibits viral entry in case of Influenza virus infection. |
17 |
|
Phyllanthus amarus Schumach. & Thonn. |
Gallotannin |
− |
+ |
+ |
5 |
1.49 |
0.59 |
Halts the process of viral replication in case of Herpes simplex virus infection. |
18 |
|
Rheum rhabarbarum L. |
Malic acid |
+ |
− |
+ |
4 |
1.91 |
0.76 |
Inhibits viral entry by ceasing the endosomal fusion in case of influenza virus. |
19 |
|
Salvia miltiorrhiza Bunge |
Salvianolic acid |
− |
+ |
+ |
5 |
1.49 |
0.59 |
Inhibition of HIV-1 integrase and protease. |
20 |
|
Taxillus sutchuenensis var. duclouxii (Lecomte) H.S.Kiu |
Butenolide |
+ |
− |
+ |
2 |
1.5 |
0.60 |
Inhibition of Hepatitis C viral NS3 serine protease and ceasing viral entry. |
21 |
|
Tinospora cordifolia (Willd.) Hook.f. & Thomson |
Tinosporaside |
+ |
+ |
+ |
5 |
2.49 |
1 |
Immunomodulatory activity; Anti-HIV activity wherein it acts as viral ribonuclease inhibitor. |
22 |
|
Withania somnifera (L.) Dunal |
Withanolide |
+ |
+ |
+ |
3 |
1.41 |
0.56 |
Disrupts interactions between viral S-protein receptor binding domain and Host ACE2 receptor. |
23 |
|
Zingiber officinale Roscoe |
6-Gingerol |
− |
+ |
+ |
5 |
1.49 |
0.59 |
Inhibits Hepatitis C virus protease. |
24 |
§Plants are selected on the basis of extensive literature surge, specifically focusing on their ethno-medicinal attributes, symptomatic relief provision abilities and direct/indirect antiviral activity, if any.
†Symbols of + and – denote the presence and absence of viral virulence factor inhibitory properties in the given plant, as deduced on the basis of keyword search matrix analysis using PubMed search engine.
*Fuzzy score μS= (S-minS)/ (maxS-minS), wherein shaded cells represent the ligands selected for further study with a fuzzy score > 0.5.
Table 4. Physicochemical properties of phytoligands in comparison with the standard chemotherapeutic agent.
|
Ligand/ Standard |
Physicochemical Properties |
||||
|
Mol. Wt. (≤ 500 D) |
Log P (≤ 5)† |
H-Bond Donor (≤ 5) |
H-Donor Acceptor (≤ 10) |
Lipinski violations (if any)* |
|
|
Allicin |
162.02 |
0.237 |
0 |
1 |
0 |
|
Amentoflavone |
538.09 |
2.030 |
6 |
10 |
1 |
|
Berberine |
336.12 |
2.473 |
0 |
4 |
0 |
|
Beta-caryophyllene |
204.19 |
6.044 |
0 |
0 |
1 |
|
11-keto-beta-boswellic acid |
470.34 |
8.131 |
2 |
4 |
1 |
|
Butenolide |
84.02 |
0.308 |
0 |
2 |
0 |
|
Citronellal |
154.14 |
3.591 |
0 |
1 |
0 |
|
Curcumin |
368.13 |
1.945 |
2 |
6 |
0 |
|
Gallotannin |
1700 |
9.537 |
25 |
46 |
4 |
|
Gamma-Glutamyl-S-allylcysteine |
290.09 |
-2.68 |
4 |
7 |
0 |
|
6-Gingerol |
294.18 |
2.437 |
2 |
4 |
0 |
|
Malic acid |
134.02 |
-1.474 |
3 |
5 |
0 |
|
β-myrcene |
136.13 |
4.170 |
0 |
0 |
0 |
|
Paeoniflorin |
480.16 |
-0.464 |
5 |
11 |
1 |
|
Quercetin |
302.04 |
1.834 |
5 |
7 |
0 |
|
Salvianolic acid |
494.12 |
2.898 |
7 |
10 |
1 |
|
Tinosporaside |
492.20 |
0.54 |
4 |
10 |
0 |
|
Withanolide |
470.27 |
3.263 |
2 |
6 |
0 |
|
Hydroxychloroquine |
335.88 |
4.00 |
4 |
2 |
0 |
†Logarithm of compound partition coefficient between n-octanol and water.
*Shaded cell indicates phytoligand with more than 1 Lipinski violations and hence is eliminated at this stage itself.
Table 5. ADMETox values of phytoligands in comparison with the standard chemotherapeutic agent.
|
Ligand/ Standard |
Absorption |
Distribution |
Metabolism |
Excretion |
Toxicity |
|||
|
Caco-2 permeability (value ≥ 0.5) |
Human intestinal absorption (value ≥ 0.5) |
Plasma Protein binding (value ≥ 0.5) |
Water solubility (logS ≥ - 4) |
P-glyco-protein activator (value ≥ 0.5) |
CYP3A4 inhibition (value ≥ 0.5) |
Acute oral toxicity (Kg/mol) (value ≥ 1.0) |
Ames test (value ≥ 0.5) |
|
|
Allicin |
0.58 (+) |
0.91 (+) |
0.50 (+) |
-0.89 (+) |
0.98 (+) |
0.92 (-) |
1.935 (-) |
0.61 (-) |
|
Amentoflavone |
0.87 (+) |
0.98 (+) |
1.11 (+) |
-3.36 (+) |
0.44 (-) |
0.61 (-) |
1.822 (-) |
0.68 (-) |
|
Berberine |
0.94 (+) |
0.77 (+) |
0.83 (+) |
-2.97 (+) |
0.68 (+) |
0.58 (-) |
1.545 (-) |
0.75 (-) |
|
Beta-caryophyllene |
0.86 (+) |
0.98 (+) |
0.83 (+) |
-4.68 (+) |
0.89 (+) |
0.86 (-) |
2.366 (-) |
0.99 (-) |
|
11-keto-beta-boswellic acid |
0.54 (+) |
0.99 (+) |
1.05 (+) |
-3.45 (+) |
0.63 (+) |
0.79 (-) |
2.834 (-) |
0.82 (-) |
|
Butenolide |
0.76 (+) |
0.96 (+) |
0.096 (-) |
0.23 (+) |
0.98 (+) |
0.98 (-) |
1.976 (-) |
0.77 (-) |
|
Citronellal |
0.92 (+) |
0.97 (+) |
0.70 (+) |
-2.44 (+) |
0.98 (+) |
0.96 (-) |
2.307 (-) |
0.99 (-) |
|
Curcumin |
0.76 (+) |
0.97 (+) |
0.83 (+) |
-3.36 (+) |
0.59 (+) |
0.53 (-) |
1.992 (-) |
0.96 (-) |
|
Gamma-Glutamyl-S-allylcysteine |
0.92 (+) |
0.63 (+) |
0.50 (+) |
-1.68 (+) |
0.93 (+) |
0.74 (-) |
1.648 (-) |
0.55 (-) |
|
6-Gingerol |
0.59 (+) |
0.99 (+) |
0.85 (+) |
-3.23 (+) |
0.89 (+) |
0.59 (-) |
2.290 (-) |
0.57 (-) |
|
Malic acid |
0.95 (+) |
0.77 (+) |
0.23 (-) |
0.27 (+) |
0.98 (+) |
0.90 (-) |
0.844 (+) |
0.87 (-) |
|
β-myrcene |
0.77 (+) |
0.96 (+) |
0.43 (-) |
-3.44 (+) |
0.98 (+) |
0.66 (-) |
1.660 (-) |
0.92 (-) |
|
Paeoniflorin |
0.82 (+) |
0.41 (-) |
0.67 (+) |
-2.97 (+) |
0.65 (+) |
0.85 (-) |
3.502 (-) |
0.53 (-) |
|
Quercetin |
0.64 (+) |
0.98 (+) |
1.17 (+) |
-2.99 (+) |
0.91 (+) |
0.69 (-) |
2.559 (-) |
0.90 (-) |
|
Salvianolic acid |
0.93 (+) |
0.96 (+) |
1.03 (+) |
-3.20 (+) |
0.65 (+) |
0.83 (-) |
2.069 (-) |
0.58 (-) |
|
Tinosporaside |
0.84 (+) |
0.83 (+) |
0.50 (+) |
-3.65 (+) |
0.54 (+) |
0.75 (-) |
3.236 (-) |
0.70 (-) |
|
Withanolide |
0.62 (+) |
0.97 (+) |
1.18 (+) |
-4.00 (+) |
0.51 (+) |
0.85 (-) |
3.660 (-) |
0.78 (-) |
|
Hydroxy-chloroquine |
0.66 (+) |
0.99 (+) |
0.86 (+) |
-4.00 (+) |
0.84 (+) |
0.83 (-) |
2.684 (-) |
0.70 (-) |
*Denoted ‘+’ or ‘-’ sign relates to the presence or absence of a predicted activity, respectively. Shaded cells indicate the descriptors violating the standard values, thereby excluding the respective phytoligand(s) from further studies.
Due to technical limitations, table 6 is only available as a download in the supplemental files section.
sodre goncalves de brito neto
ORCiDcommented on 19 May, 2020
Maravilhoso trabalho!!!