Figure 4.
Various phytoconstituents have been effectively screened in silico for their antiviral properties and hundreds of phytocompounds have been reported with inhibitory activity against various COVID-19 targets like Mpro, ACE2, spike glycoproteins, and nucleocapsid proteins amongst others. A variety of phytochemicals like Mangiferin, Azithromycin, Procyanidin-Β-2,7-Dimethox-Yflavan-4′-O-Β-D-Glucopyranoside, Amentoflavone, Hidrosmin, Diosmin, Gallocathechin Gallate, Elsamitrucin, Pectolinaren, Quercetin and Iso-Quercetin have been studied as Mpro inhibitors using computational analyses.
Flavonoid based compounds like Rutin, Isorhamnetin-3-O-Β-D and Calendoflaside extracted from Calendula officinals have also shown inhibitory activity against Mpro of which Rutin is already in use as a drug and the other two can be expected to be available soon. Based on bioactivity, binding mode, and various molecular interaction, Lupeol(–8.6 Kcal/Mol), Lupenone (–7.7kcal/Mol), Hesperetin(–7.4 Kcal/Mol), Apigenin (–7.3 Kcal/Mol), and Castasterone (–7.3 kcal/mol) were identified as probable inhibitors of SARS-CoV-2, and were reported to have better inhibitory activity as compared to Remdesivir and Azithromycin .
Molecular docking studies have shown that alkaloids like Berberine, Tetrahydropalmatine, Tryptanthrine, Indirubin, Indigo, Indican and 5ar-Ethyltryptanthrin are potential COVID-19 inhibitors that majorly target either 3CLpro or Mpro of SARS-CoV-2 . Quinoline and Quinazoline alkaloids like Oxoglyantrypine, Norquinadoline A, 3-Hydroglyantrypine, Deoxytrytoquivaline, Deoxynortryptoquivaline and Neosartoryadin A were reported to exhibit inhibitory activity against COVID-19 using molecular docking studies followed by toxicity and drug likeness analysis . In addition,Quinacrine, Quinidine and Quinine (from Cinchona officinalis ), Chlorogenic acid and Hesperidin extracted fromZingiber officinale , Luteolin-7-O-glucuronide extracted fromOcimum sanctum , Epigallocatechin-3-gallate (EGCG), Theaflavin gallate, Fisetin, Anisotine extracted from Justicia adhatoda , Thalimonine, Sophaline D , Bromhexine (from Adhatodavasica ), Castanospermine (from Castanospermum australe ), Cepharanthine (from Stephania spp .), Hernandezine (from Thalictrum podocarpum ), Homoharringtonine (from Cephalotoxusharringtonia ), Hydroquinidine (from Cinchona officinalis ), Isoliensinine and Liensinine (from Nelumbo nucifera ), Lycorine (fromAmaryllidaceae spp. ), Neferine (from Nelumbo nucifera ), Oxysophoridine (from Sophora alopecuroides ),Reserpine (fromRauwolfia serpentina ), Tetrandrine (from Stephania tetrandra ), Myristicin extracted from Myristica fragrans,Cannabinoids extracted from Cannabis spp. , Rhoifolin and Eugenol extracted from Syzygiumaromaticum, 6-Shogaol from Zingiber officinale and Ethyl cholate from Pangiumedule also form a majority of the compounds that have been studied through molecular docking and dynamics-based simulation analysis. These compounds have shown excellent binding affinity with various SARS-CoV-2 drug targets. However, to test their reported biological properties, validation through in vitro and clinical studies is required.