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Table 1 Drugs aiming at the proliferation process

From: Human coronaviruses and therapeutic drug discovery

Step Target Drugs Type Reference number
Category Example
Attachment and entry Block receptor binding S1-RBD mAbs m336, m337 and m338 MERS-CoV [9]
Human-derived SARS mAbs SARS-CoV [10, 11]
Receptor-derived proteins P4 and P5 peptides SARS-CoV [12]
Receptor ACE2 antagonist NAAE SARS-CoV [13]
DPP4 antagonist Adenosine deaminase, anti-DPP4 mAbs MERS-CoV [14, 15]
Oligosaccharide-rides on S Antiviral protein Griffithsin SARS-CoV, MERS-CoV, HCoV‑229E, HCoV‑OC43 [16]
Block endocytosis Host proteases that cleavage S protein TMPRSS2 inhibitor Camostat, nafamostat SARS-CoV,; MERS-CoV [17, 18]
Cathepsin L inhibitor Teicoplanin, dalbavancin SARS-CoV, MERS-CoV, SARS-CoV-2 [19]
HR1/HR2 Peptide HR2P and P1 peptide MERS-CoV [20, 21]
229E-HR1P and 229E-HR2P HCoV-229E [22]
OC43-HR2P Broad spectrum [23]
Viral envelope Antiviral drug arbidol Broad spectrum [24]
Small molecules LJ001 [25]
NHR trimeric coiled coils α-helical lipopeptides MERS-CoV [26]
Endosomal acidification Antimalarial Chloroquine, chloroquine phosphate SARS-CoV-2 [30,31,32]
Clathrin-mediated endocytosis Antagonist of DA receptor Chlorpromazine MERS-CoV [30]
Replicase protein expression PLpro; (Papain-like protease); (nsp3) Thiopurine analogs 6-mercaptopurine (6MP) and 6-thioguanine (6TG) MERS-CoV [33]
Immunosuppressive drug Mycophenolic acid MERS-CoV [33]
Alcohol-aversive drug Disulfiram SARS-CoV, MERS-CoV [34]
Protease inhibitor Zinc ion (Zn2+) and zinc conjugate inhibitors SARS-CoV [35]
Compound F2124-0890 SARS-CoV, MERS-CoV [36]
Mpro; (3C-like protease); (nsp5) Peptidomimetic inhibitors of enterovirus 3Cpro 6b, 6c and 6d SARS-CoV, MERS-CoV [37]
1,2,3-triazole derivatives Compounds 14d, 14n, 14q, 18f and 18i HCoV-229E [38]
Protease inhibitor Lopinavir/ritonavir SARS-CoV, MERS-CoV, HCoV-229E [30, 39, 46, 48, 49]
Darunavir/cobicistat SARS-CoV-2 NCT04252274
Protease inhibitor Ti-containing polyoxometalates (POMs) SARS-CoV [40]
Derivates of pyrithiobac (PTB) Compound 6–5 SARS-CoV [41]
Peptide; mimic inhibitor N3 Broad spectrum [42]
Synthesized compounds Derivates of isatin, piperazineare and phenylisoserine SARS-CoV [44, 45]
Derivates of piperidine MERS-CoV [43]
Replication, transcription and translation NSPs NSP12 RdRp inhibitor Remdesivir Broad spectrum [50,51,52,53,54]
Doubly flexible nucleoside analogues such as compound 2 Broad spectrum [55]
Galidesivir (synthetic adenosine analogue) Broad spectrum [56]
6′-fluorinated-aristeromycin analogues Broad spectrum [57]
Favipiravir broad spectrum [58, 59]
NSP13 Helicase inhibitor Aryl diketoacids (ADK), SSYA10-001, halogenated triazole compounds SARS-CoV, MERS-CoV [61, 62, 65]
NTP enzyme inhibitor Bananins, 2,6-bis-arylmethyloxy-5-hydroxychromones SARS-CoV, SARS-associated CoV [63, 64]
NSP16 Drug targeting SAM S-adenosine-1 homocysteine SARS-CoV, HCoV 229E [66]
Paclitaxel [66]
Aurintricarboxylic acid (ATA) [66]
Drug interfering with the binding of NSP16 to NSP10 The peptide chain reversely designed according to the sequence of nsp16′s binding domain [66]
Host signaling pathways Cyclophilin inhibitors Cyclosporine, alisporivir SARS-CoV, MERS- CoV, HCoV-NL63 [67,68,69]
Kinase signal transduction inhibitors Trametinib, imatinib MERS-CoV [3, 70]
Viral nucleic acid or RNA synthesis complex siRNA Specific siRNAs targeting the S/M/E/N/accessory protein gene SARS-CoV, MERS-CoV [71,72,73,74,75,76]
Immunosuppressive drug Mycophenolic acid MERS-CoV [77]
Ribozyme Synthetic chimeric DNA–RNA hammerhead ribozyme SARS-CoV [78]
Synthesis K22 (targeting membrane-bound viral RNA) Broad spectrum [79]
Apoptosis inducer dsRNA-activated caspase oligomerizer (DRACO) Broad spectrum [80]
N protein Compound N-(6-oxo-5,6-dihydrophenanthridin-2-yl) (N,N-dimethylamino)acetamide hydrochloride (PJ34) HCoV-OC43 [81]
Intrabody Fibronectin-based intrabodies SARS-CoV [82]
Inhibitor Resveratrol MERS-CoV [83]
Assembly and release E protein Ion channel blocker Hexamethylene amiloride HCoV-229E [84]
Cytoskeleton Filament depolymerizing drug NOC (nocodazole) HCoV-229E, HCoV-NL6 [3, 85]
  1. RBD: receptor binding domain; mAbs: monoclonal antibodies; SARS: Severe acute respiratory syndrome; MERS: Middle East respiratory syndrome; ACE2: Angiotensin converting enzyme 2; DPP4: dipeptidyl peptidase 4; NHR: N-terminal heptad repeat; HR1: Heptad repeat 1 domain; HR2: Heptad repeat 2 domain; DA: dopamine; 6MP: 6-mercaptopurine; 6-TG: 6-thioguanine; Zn2+: zinc ion; POM: polyoxometalate; PTB: derivates of pyrithiobac; NAAE: N-(2-aminoethyl)-1-aziridineethanamine; TMPRSS2: transmembrane protease serine 2; Nsps: non-structural proteins; RdRp: RNA-dependent RNA polymerase; ADK: aryl diketoacids; NTP: nucleoside triphosphate; SAM: S-adenosyl-l-methionine; ATA: aurintricarboxylic acid; dsRNA: double-stranded RNA; DRACO: dsRNA-activated caspase oligomerizer; siRNA: small interfering RNAs; PJ34: N-(6-oxo-5,6-dihydrophenanthridin-2-yl) (N,N-dimethylamino) acetamide hydrochloride; NOC: nocodazole