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.