Table 2.
Potential inhibitors of SARS-CoV-2 3CLpro selected from existing databases or literature.
| Source | Number | Method | Potential inhibitor |
|---|---|---|---|
| ZINC | 2,000 [150] | VS | ZINC32960814/12006217/03231196/33173588 |
| 1,500a[151] | ZINC20291569/90403206/95480156 | ||
| 5,811b[152] | SCAR protocol | Telcagepant; Vidupiprant; Poziotinib; Fostamatinib. | |
| 606 million [153] | VS; MD simulations |
(−)-Taxifolin; Rhamnetin | |
| 1,000c[154] | ZINC000621278586/000621285995 | ||
| Asinex; ChEMBL | > 8,722 [155] | BBB_26580140; SCHEMBL12616233/18616095/20148701 | |
| SuperNatural II; In-house database; SuperDrug2; WithDrawn |
360,000 [156] | SN00017653 (SuperNatural II); Pseudostellarin C (in-house); Eledoisin (SuperDrug2); Naldemedine (SuperDrug2); Saralasin (WithDrawn); Saquinavir (WithDrawn) |
|
| Chemical Abstract Services | 35,000 [157] | SKS-01; SKS-02; SKS-03; SKS-04; | |
| Literatures; PubChem; Asinex |
> 10,584d[158] | pq8; pq9; pq10; A12 Note: Structures of these inhibitors are shown in Fig. S2. |
|
| Protein Data Bank | 2,692 [159] | PubChem IDs: 118098670; 104161460; 163632044 | |
| Literature | 49e[160] | Ethaselen (IC50 = 4.51 μM) | |
| PubChem | 10,433f[161] | 6-Deaminosinefungin; UNII-O9H5KY11SV | |
| Life Chemicals; Asinex | 21,207g[162] | F2679-0163(Life chemicals); F6355-0442 (Life chemicals); 8250 (Asinex) | |
| Pharmit | 213.5 million [163] | CSC057752019; PubChem-22029441/-11210821; MCULE-9349798441; MolPort-045-918-905 |
|
| DrugBank; Literatures; In-house database |
2,736h[164] | Acteoside; Chebulinic acid; Delphinidin-3,5-diglucoside; Saquinavir; Lithospermic acid B; 11m_32045235 |
|
| DrugBank | 10,036b[165] | DB02388; Cobicistat | |
| 10,246 [166] | Levothyroxine; Amobarbital; ABP-700 | ||
| 13,227 [167] | VS | DB02128/01871/04502/02378/03063/04378/03648/04353/04692/047https://doi.org/10/08732/11938/03395/04653/04758/07571/07934/12955;DBMET00084/01550/01549/01548 | |
| ChEMBL | 1,485,144 [168] | CHEMBL1559003/2237553/1511674/3260476/1170272/1335000/2235580/3264032/1447105/589899/1539803/2216842/427787/1339675/3126648/1302388/3234783/1807774/2087984/2387487/2113271/476947/399042/2000247/3236740/1447944/1760165/2087965 | |
| 33 protease inhibitors [169] | Paritaprevir; Ciluprevir; Simeprevir; Deldeprevir; Indinavir; Saquinavir; Faldaprevir; Brecanavir; Grazoprevir; Lopinavir |
||
| Protein Data Bank; SwissSimilarity |
133i[170] | Melatonin | |
| Existing drug database | > 2,500 [171] | VS; MD simulations; Experimental evaluation |
Dipyridamole (Ki = 0.04 μM); Hydroxychloroquine (Ki = 0.36 μM); Chloroquine (Ki = 0.56 μM) |
| LASSBio | 2,300 [172] | VS; Experimental evaluation |
LASSBio-1945 (IC50 = 15.97 μM) |
| DrugBank; PubChem | 5,016j[173] | HTVS; MD simulations | Isavuconazonium; α-KI; Pentagastrin |
| Compound Library | 23,000 [174] | HTVS | Azanitrile (Ki = 24.0 nM); Pyridyl ester(Ki = 10.0 nM) |
| In-house database; TargetMol; Selleckchem; Antivirus Drug Library |
~ 10,000 [54] | HTVS; VS; Experimental evaluation |
Ebselen (IC50 = 0.67 μM); Disulfiram (IC50 = 9.35 μM); Tideglusib (IC50 = 1.55 μM); Carmofur (IC50 = 1.82 μM); Shikonin (IC50 = 15.75 μM); PX-12 (IC50 = 21.39 μM) Note: These inhibitors have been further confirmed [175], [176], [177], [178], [179]. |
| AVPdb database | 88 [180] | Molecular docking; MD simulations |
P14, P39, P41, P74 Note: Sequences of these inhibitors are shown in Table S7. |
Note: The binding mechanisms of all inhibitors to 3CLpro are listed in Table S6.
These compounds were selected according to the pharmacophore features of inhibitor N3.
Approved or investigational drugs.
Protease-inhibitor-like compounds.
Analogs of Chloroquine.
Se-containing heterocyclic compounds.
The compounds that have > 90% structural similarity with the 10 high-affinity molecules previously reported (PubChem IDs: 5281605, 16394003, 19323586, 44137675, 118737648, 787400, 8386889, 34755, 65482 and 145998233).
12,485 anti-SARS-CoV-2 or antiviral compounds in the Life Chemicals database and 8,722 antiviral compounds in Asinex database.
2,454 FDA approved drugs from DrugBank, 144 coronavirus Mpro inhibitors from published literature and 138 natural compounds from an in-house database.
74 ligand-Mpro complexes and 59 analogues.
6 analogs of SARS-CoV-2 3CLpro inhibitor (13b) [58] in DrugBank and 5,010 analogs of 11 antiviral agents (Atazanavir, Darunavir, Fosamprenavir, Indinavir, Lopinavir, Ritonavir, Saquinavir, Tipranavir, Delavirdine, Nevirapine and Remdesivir) in PubChem.