Table 3.
Compilation of key in silico-based studies undertaken to identify the best leads from the natural products arena against SARS-CoV-2.
| Group [Ref] | Target | Database/natural compounds (n) | Methodology | Outcome (best in silico leads) |
|---|---|---|---|---|
| Ghosh et al., (Ghosh et al., 2021) | Mpro | 113 Compounds of natural origin inhibiting Mpro in SARS-CoV were retrieved, and 88 compounds were further considered for current work on the basis of available IC50 and binding affinity data | QSAR based data mining followed by structural and physiochemical interpretation (SPCI) analysis | Rutin, Hespiridine, 22-Hydroxyhopan-3-one, Oolonghomobisflavan-A, Theasinensin-D, Quercetin, 3-vicianoside, Deacetylcentapicrin, Kouitchenside, Neohesperidin, Lignan, Myricitrin, Baicalin, Cyanidin 3-glucoside |
| Cheke et al., (Cheke et al., 2020) | Spike glycoproteins and ACE2 | 12 Natural compounds with reported antiviral attributes | Molecular docking | Indigo blue, glycyrrhizin, β-sitosterol, indirubin, bicylogermacrene, curcumin, hesperetin, rhein, and berberine |
| Sahin et al., (Sahin et al., 2021) | Mpro | Didemnins A, B and C | Molecular docking | Didemnin B |
| Monajjemi et al., (Monajjemi et al., 2020) | Protease | Vidarabine, Cytarabine, Gemcitabine, and Matrine extracted from Gillan's leaves plants. | Docking simulation and NMR investigation | Cytarabine |
| Saeed et al., (Saeed et al., 2020) | Endoribonuclease NSP15 | 1624 Natural compounds (NuBBE database) | Virtual screening and molecular docking, followed by molecular dynamics for top leads | NuBBE-1970 and NuBBE-242 |
| Caruso et al., (Caruso et al., 2020) | Mpro | Quinone derivatives | Molecular docking and DFT | Embelin |
| Basu et al., (Basu et al., 2020) | Spike protein and human ACE2 | 5 (Flavonoid and anthraquinone subclass) | Homology modelling, Molecular docking | Hesperidin |
| Gopinath et al., (Gopinath et al., 2020) | SARS-CoV-2–ACE2 Receptor Interface | ZINC biogenic (206,800 compounds) FooDB (18,477 compounds), Molport Natural Compound and Natural-Like Compound Database (119,054 compounds), and Super Natural II database (267,762) | Molecular dynamics simulations (MixMD) with high-throughput virtual screening (HTVS) | ZINC000002128789 |
| Al-Sehemi et al., (Al-Sehemi et al., 2020) | Spike glycoprotein | 31000 NPASS library | Virtual screening and molecular docking | Castanospermine and karuquinone B |
| Ibrahim et al., (Ibrahim et al., 2020b) | Mpro | 32 Natural spices (Isolated from 14 cooking seasonings) | Molecular docking, dynamics and Born surface area energy calculations | Salvianolic acid A |
| Kumar et al., (Chidambaram et al., 2020) | Mpro | 11 Natural coumarin analogues | Molecular docking | Toddacoumaquinone |
| Khalifa et al., (Khalifa et al., 2020) | CLpro | 10 Poly-acylated anthocyanins derivatives | Molecular docking | Phacelianin |
| Naik et al., (Naik et al., 2020) | Helicase, Endoribonuclease, Exoribonuclease, RNA-dependent RNA Polymerase, Methyltransferase, 3C-like proteinase |
3963 Compounds from the NPASS database | Virtual screening, molecular docking and Dynamics | NPC214620, NPC52382, and NPC270578 |
| Narkhede et al., (Narkhede et al., 2020) | Mpro | 12 Compounds from the PubChem database | Molecular docking | Glycyrrhizin and Rhein |
| Abdelrheem et al., (Abdelrheem et al., 2020) | Mpro | 10 Compounds from plants or marine algae | Molecular docking and dynamics | Caulerpin |
| Ananth et al., (Vivek-Ananth et al., 2020) | TMPRSS2 and cathepsin L | 14,011 Phytochemicals produced by Indian medicinal plants | Virtual screening, Molecular docking and dynamics | TMPRSS2: Qingdainone, Edgeworoside-C and Adlumidine; CathepsinL: Ararobinol, (+)-oxoturkiyenine and 3α,17α-cinchophylline. |
| Rakib et al., (Rakib et al., 2020) | Mpro | 309 Compounds eluted from methanol extract of T. crispa in GCMS, Lipinski rule applied to 309 compounds and 56 were selected for in silico study | Molecular docking | imidazolidin-4-one, 2-imino-1-(4-methoxy-6-dimethylamino-1,3,5-triazin-2-yl) |
| Alamri et al., (Alamri et al., 2020) | RdRp; 3CLpro; PLpro | ~1000 Compounds available in the in-house database from traditional Saudi medicinal plants | Virtual screening, Molecular docking |
RdRp: Luteolin 7-rutinoside, chrysophanol 8-(6-galloylglucoside) and kaempferol 7-(6″-galloylglucoside); 3CLpro: Chrysophanol, 3,4,5-tri-O-galloylquinic acid and mulberrofuran G; PLpro: Withanolide A, isocodonocarpine and calonysterone |
| Qamar et al., (Tahir Ul Qamar et al., 2020) | 3CLpro | 32,297 Potential antiviral phytochemicals/traditional Chinese medicinal compounds | Virtual screening, molecular docking and dynamics | Myricitrin and methyl rosmarinate |
| Mazzini et al., (Mazzini et al., 2020) | Mpro | 135 Natural and nature-inspired compounds | Virtual screening, Molecular docking | Camptothecin, leopolic acid, and lamellarin D |
| Sayed et al., (Sayed et al., 2020) | Mpro | >24,000 Compounds from a library of natural microbial products | Hyphenated pharmacophoric-based and structural-based virtual screening followed by molecular dynamics | Citriquinochroman, Holyrine B, Proximicin C, Pityriacitrin B, (+)-anthrabenzoxocinone, penimethavone A |
| Olubiyi et al., (Olubiyi et al., 2020) | 3CLpro | 3200 Natural compounds from Nigerian plants | Virtual screening and molecular docking | Theacitrin A, corilagin, theaflavin, amentoflavone, epigallocatechin gallate (EGCG), and neodiosmin |
| Subbaiyan et al., (Subbaiyan et al., 2020) | S-protein | 12 Ligands of herbal origin | Molecular docking | Epigallocatechin |
| Owis et al., (Owis et al., 2020) | Mpro | 11 Flavonoid glycosides were identified from S. persica aerial parts (stem and leaves) on the basis of metabolic profiling (secondary metabolites) | Molecular docking | Narcissin, Kaempferol-3-O-α-l-rhamnopyranosyl-(1 → 6)-β-d-glucopyranoside |
| Rahman et al., (Rahman et al., 2020) | TMPRSS2 | 30,927 Compounds from NPASS library | Ligand-based pharmacophore approach and molecular docking | NPC306344 |
| Gentile et al., (Gentile et al., 2020) | Mpro | 14,064 Marine dataset molecules retrieved from http://docking.umh.es/downloaddb | Pharmacophore filter, virtual screening, molecular dynamics and redocking | Phlorotannin, 1,3,5-trihydroxybenzene |
| Fakhar et al., (Fakhar et al., 2020) | 3CL hydrolase protein | 3435 Anthocyanin derivatives from PubChem database | Virtual screening, molecular docking and dynamics | PubChem IDs 44256891, 44256921, 102452140, 131751762, 131831710 and 139031086 |
| Selvaraj et al., (Selvaraj et al., 2020) | NSP14 | 22122 Compounds from TCM Database | Virtual screening, molecular docking and dynamics | TCM 57025, TCM 3495, TCM 5376, TCM 20111, and TCM 31007 |
| Joshi et al., (Joshi et al., 2020) | Mpro | ~7100 Phytochemicals belonging to alkaloids, flavonoids, glucosinolates, phenolics, terpenes and terpenoid category | Phylogenetic analysis by maximum likelihood (ML) method followed by virtual screening and molecular docking | δ-Viniferin, myricitrin, chrysanthemin, taiwanhomoflavone A, Lactucopicrin 15-oxalate, nympholide A, afzelin, biorobin, hesperidin and phyllaemblicin B |
| Kumar et al., (Kumar et al., 2020) | Mpro | 274,363 Compounds, among which 120,720 belong to Zinc natural database and 14,064 to Marine Natural Products (MNP) database | Pharmacophore based virtual screening, molecular docking, molecular dynamics and MM-GBSA approach | SN00293542 and SN00382835 |
| Ibrahim et al., (Ibrahim et al., 2020a) | Mpro | 113,756 Natural and natural-like products from MolPort database | Molecular docking, followed by molecular dynamics and MM-GBSA binding energy calculations | MolPort-004-849-765, MolPort-000-708-794, MolPort-002-513-915 and MolPort-000-702-646 |
| Sharma et al., (Sharma and Shanavas, 2020) | Mpro and ACE2 | 60 Compounds, among which 30 were natural secondary metabolites | Molecular docking, followed by MM-GBSA binding energy calculations | Delphinidin 3,5-diglucoside, Scutellarein 7-glucoside, Avicularin and 3,5-Di-O-galloylshikimic acid |
| Chidambaram et al., (Chidambaram et al., 2021) | Mpro | 10 Compounds, Calanolide A, Cardatolide A, Collinin, Inophyllum A, Mesuol, Isomesuol, Pteryxin, Rutamarin, Seselin, Suksdorin, | Molecular docking | Inophyllum A |
| Khan et al., (Khan et al., 2020) | Mpro | 5 Marine compounds | Molecular docking and dynamics | CID 11170714 |
| Chikhale et al., (Chikhale et al., 2020) | TMPRSS2 | 2230 Natural-based compounds from the Selleckchem database | Homology modelling, virtual screening and molecular dynamics | Neohesperidine, Myricitrin, Quercitrin, Naringin, and Icariin |
| Pandey et al., (Pandey et al., 2020) | Spike protein | 11 Natural compounds | Molecular docking and dynamics | Kaempferol, quercetin, and fisetin |
| Sepay et al., (Sepay et al., 2020) | Mpro | 50 Natural products derived compounds | DFT, molecular docking and dynamics | Terpenoid (T3) from marine sponge Cacospongia mycofijiensis |
| Gahlawat et al., (Gahlawat et al., 2020) | Mpro | Three datasets belonging to natural products isolated from diverse families of plants, Mpro inhibitors from the literature and the FDA approved drugs were employed | Virtual screening, molecular docking and dynamics | The literature of Mproinhibitor: lithospermic acid B, Rutin, neonuezhenide Natural product database: chebulinic acid, delphinidin-3,5-diglucoside, cyanidin-3,5-diglucoside, acteoside |
| Iheagwam et al., (Iheagwam and Rotimi, 2020) | PLpro, 3CLpro), RdRp, 2OMT, S-RBD, ACE2, and TMPRSS2 | 65 African natural products from the ZINC database | Molecular docking | 3-galloylcatechin, proanthocyanidin B1, and luteolin 7-galactoside |
| Lakshmi et al., (Alagu Lakshmi et al., 2020) | Mpro, spike protein and ACE2 | 47 Ligands from 10 ethnomedicine plant of Indian origin | Molecular docking and dynamics | Cucurbitacin E, Orientin, Bis-andrographolide, Cucurbitacin B, Isocucurbitacin B, Vitexin, Berberine, Bryonolic acid, Piperine and Magnoflorine |
| Gyebi et al., (Gyebi et al., 2020) | 3CLpro | 62 Bioactive alkaloids and 100 terpenoids African plants | Molecular docking |
Alkaloids: 10-Hydroxyusambarensine, and Cryptoquindoline; Terpenoids: 6-Oxoisoiguesterin and 22-Hydroxyhopan-3-one |
| Majumdar et al., (Majumder and Mandal, 2020) | Mpro | Initial search for Mpro lead was done from the Sigma-Aldrich plant profiler chemical library. This search led to the identification of Rutin, and 40 similar pharmacophores were retrieved from the SwissSimilarity web tool | Molecular docking and dynamics | Peonidin 3-O-glucoside, Kaempferol 3-O-β–rutinoside, 4-(3,4-Dihydroxyphenyl)-7-methoxy-5-[(6-O-β-D-xylopyranosyl-β-D-glucopyranosyl)oxy]-2H-1-benzopyran-2-one, Quercetin-3-D-xyloside, and Quercetin 3-O-α-L-arabinopyranoside |