Table 1.
List of some promising natural compounds and their analogues that are discussed in the text is documented along with their potent in vitro anti-SARS-CoV-2 activity in virus-infected host cells and their major therapeutic targets against SARS-CoV-2 via inhibition of the activity of host/virus proteases.
| Natural compound/synthetic analogue | In vitro inhibition of SARS-CoV-2 infection/replication in host cells | Major therapeutic targets against SARS-CoV-2 via inhibition of host/virus protease activity | Reference (s) |
|---|---|---|---|
| Plitidepsin 7 | IC90 of 1.76 nM in Vero E6 cells and 0.88 nM in hACE2/293T cells as compared to remdesivir (IC90 of 2.25 μM and 24.20 nM, resp.) | Inhibits the activity of host eEF1A protease | [41] |
| Silvestrol 8 | Abolishes replication completely at 100 nM in human bronchial epithelial cells | Inhibits the activity of eIF4A protease, N and nsp8 proteins | [45,46] |
| Zotatifin 9 | IC90 of 37 nM in Vero E6 cells | Inhibits the activity of host eIF4A protease | [30] |
| CR-31-B-(−) 10 | EC50 of 1.82 nM in Vero E6 cells | Inhibits the activity of EIF4A and N proteins | [45] |
| Emetine 11 | EC50 of 0.147 nM in Vero E6 cells and SI of 10910.4 as compared to remdesivir (EC50 of 0.24 μM); IC50 of 0.2729 μM in 293T cells in suppression of virus RNA copies | Inhibits the activity of S, eIF4E, RdRp, N and orf6 proteins | [33,[53], [54], [55], [56], [57], [58]] |
| Cepharanthine 12 | IC50 of 1.90 μM in Vero E6 cells and at 10 μM completely abolished the viral replication in Vero E6 cells | Inhibits the activity of S and NPC-1 proteins | [60] |
| Tetrandrine 13 | IC50 of 10.37 μM in Vero E6 cells | Inhibits the activity of S and TPC-2 proteins | [60] |
| Gallinamide A 14 | EC50 of 28 nM in Vero E6 cells and CC50 of >100 μM | Inhibits the activity of cathepsin L with IC50 of 17.6 pM | [65] |
| Synthetic analogue 15 | EC50 of 168 nM in Vero E6 cells and CC50 of >100 μM; completely inhibits the virus infection in ACE2/A549 cells at 310 nM concn | Inhibits the activity of cathepsin L with IC50 of 5.6 pM | [65] |
| Synthetic analogue 16 | EC50 of 920 nM in Vero E6 cells; completely inhibits the CPE in ACE2/A549 cells at 310 nM concn | Inhibits the activity of cathepsin L with IC50 of 17.0 pM | [65] |
| Apratoxin S4 18 | IC50 of 170 nM and 0.71 nM in Vero E6 and hACE2/HeLa cells, resp. and SI of >58 and > 1400 resp.; completely inhibits the viral replication in hACE2/HeLa cells at 2 nM concn | Inhibits the activity of host Sec61 protease | [68] |
| Baicalein 19 | EC50 of 2.94 μM in Vero E6 cells and SI of >172; EC50 of 1.2 μM in Calu-3 cells and CC50 of 91 μM | Inhibits the activity of virus Mpro with IC50 of 0.39 μM; of virus RdRp and helicase nsp13 | [[69], [70], [71], [72]] |
| Quercetin 21 | IC50 of 192 μM in Vero E6 cells and CC50 of 500 μM | Inhibits the activity of virus Mpro with an IC50 of 21 μM and of virus helicase unwinding activity with IC50 of 0.53 μM | [72,75] |
| Quercetin analogue 22 | IC50 of 8 μM in Vero E6 cells and CC50 of 100 μM | Inhibits the activity of virus Mpro with an IC50 of 11 μM | [75] |
| Curcumin 23 | EC50 of 4.06 μM and 1.14 μM against virus D614G and Delta strains in Vero E6 cells, resp; completely inhibits the CPE of these strains at 10 μg/ml concn | Inhibits the activity of virus Mpro with an IC50 of 11.9 μM | [78,81] |
| Homoharringtonine 24 | EC50 of 2.14 μM in Vero E6 cells; IC50 of 30 nM in pseudovirus entry in Caco-2 cells | Inhibits the activity of host TMPRSS2 and eIF4E proteases | [53,89,90] |