actually, those 95 authors did provide a table of the drugs they’ve tested which show promise against coronavirus. Here it is. I fear the structure of the table has not survived the paste. I refer the interested reader back to the URL in my last blog post. Take it as a demonstration of the amazing array of stuff out that that may be able to corral our annoying little visitor.
Table 1a. Literature-deriveda drugs and reagents that modulate SARS-Cov-2 interactors.
Compound Name
Compound Structure
Human Gene
Viral Bait Drug Status
Activity (nM)
Silmitasertib106,107
CSNK2A2 N
Approved (Cancer)
CK2 inhibitor IC50 = 1
TMCB108 CSNK2A2 N
Pre-clinical
Multi-targeted protein kinase inhibitor
Ki = 21
Apicidin109 HDAC2 Nsp5 Pre-clinical HDAC inhibitor IC50 = 120
Valproic Acid110,111 HDAC2 Nsp5
Approved (CNS
diseases, Cancer)
HDAC2 inhibitor Ki = 5
Bafilomycin A1112 ATP6AP1 Nsp6 Pre-clinical ATPase inhibitor IC50 = 100
E-52862113 SIGMAR1 Nsp6 Clinical Trial Sigma 1 antagonist IC50 = 17
PD-144418114 SIGMAR1 Nsp6 Pre-clinical Sigma 1 antagonist Ki = 0.8
RS-PPCC115 SIGMAR1 Nsp6 Pre-clinical Sigma 1 agonist Ki = 1.5
PB28
SIGMAR1
116 TMEM97
Nsp6 Pre-clinical Orf9c
Sigma 1/2 modulator IC50 = 15
117 SIGMAR1
Nsp6
Approved
Sigma 1/2 modulator
Haloperidol
TMEM97
Orf9c
(CNS
diseases)
Ki = 2-12
Entacapone
118,119
COMT Nsp7
Approved (Parkinson’s disease)
COMT inhibitor IC50 = 151
Indomethacin120 PTGES2 Nsp7
Approved (Inflammation, Pain)
Prostaglandin E2 synthase inhibitor IC50 = 750
Metformin121 NDUFs Nsp7
Orf9c
Approved (Diabetes)
MRC 1 inhibitor (indirect)
Ponatinib122 RIPK1 Nsp12 Approved (Cancer)
RIPK1 inhibitor IC50 = 12
H-89123 PRKACA Nsp13 Pre-clinical
Protein kinase A inhibitor
KD = 48
Merimepodib124 IMPDH2 Nsp14 Clinical Trial IMPDH inhibitor Ki = 10
Migalastat
125
α-Gal inhibitor IC50 = 40
Mycophenolic acid
126
IMPDH inhibitor IC50 = 20
| GLA Nsp14 Approved (Fabry disease) IMPDH2 Nsp14 Approved (Organ rejection) |
Ribavirin127 IMPDH2 Nsp14 Approved (Viral infection)
IMPDH inhibitor IC50 = 100-250
XL413128 DNMT1 Orf8 Clinical Trial CDC7 inhibitor IC50 = 3.4
CCT 365623129 LOX Orf8
Pre-clinical
LOXL2 inhibitor IC50 = 1500
Midostaurin130 MARK2/3 Orf9b Approved (Cancer)
Protein kinase inhibitor MARK1
KD = 100 MARK3 KD = 23
Ruxolitinib
131
MARK2/3 Orf9b
Approved (Myelofibrosis)
Protein kinase inhibitor MARK1
KD = 660 MARK3
KD > 10000
ZINC1775962367132 DCTPP1 Orf9b Pre-clinical
ZINC4326719133 DCTPP1 Orf9b Pre-clinical
ZINC4511851134 DCTPP1 Orf9b Pre-clinical
dCTPase inhibitor IC50 = 47
DCTPP1 inhibitor IC50 = 19
dCTPase inhibitor IC50 = 20
ZINC95559591
135 MARK3
TBK1
Orf9b Pre-clinical Nsp13
Protein kinase inhibitor MARK3 IC50 = 12
TBK1 IC50 = 6
AC-55541136 F2RL1 Orf9c Pre-clinical
AZ8838137 F2RL1 Orf9c Pre-clinical
PAR agonist pEC50 = 6.7
PAR antagonist IC50 = 344
Daunorubicin
138
ABCC1 Orf9c
Approved (Cancer)
Topoisomerase inhibitor
Ki = 70
GB110139 F2RL1 Orf9c Pre-clinical PAR2 agonist EC50 = 280
S-verapamil140
ABCC1 Orf9c
Approved (Hypertension)
Ca2+ channel inhibitor and drug efflux transporter inhibitor
Ki = 113
AZ3451137 F2RL1 Orf9c Pre-clinical
PAR2 negative allosteric modulator pKD = 15
- These drug-target associations are drawn from chemoinformatic searches of the literature, drawing on databases such as ChEMBL141, ZINC142 and IUPHAR/BPS Guide to Pharmacology143
Table 1b. Expert-identifieda drugs and reagents that modulate SARS-CoV-2 interactors.
Compound Name
Compound Structure
Human Gene/ Process
Viral Bait
Drug Status
Activity (nM)
ABBV-74468 BRD2/4 E Clinical Trial
| Degrades BRD BRD2/4 E Pre-clinical proteins IC50 < 10000 |
dBET6144
BRD
inhibitor KD = 2.1
MZ1145 BRD2/4 E Pre-clinical
| BRD2/4 inhibitor BRD2 BRD2/4 E Clinical Trial IC50 = 25 BRD4 IC50 = 18 |
CPI-0610146
Degrades BRD
proteins KD = 120-
228
Sapanisertib87,147 LARP1 N Clinical Trial
mTOR
inhibitor IC50 = 1
Rapamycin87,148
LARP1 FKBP15 FKBP7/10
N
Nsp2 Orf8
Approved (Organ rejection)
mTOR
inhibitor (with FKBP) IC50 = 2.0
149 EIF4E2/H Nsp2 Clinical Trial EIF4a
Zotatifin
inhibitor IC50 = 1.5
Verdinexor
NUPs
150 RAE1
Nsp4 Nsp9 Orf6
Clinical Trial
XPO1
nuclear export inhibitor IC50 = 960
Chloroquine151 SIGMAR1 Nsp6
Approved (Malaria)
Sigma 1 binder Ki = 100
Dabrafenib152 NEK9 Nsp9 Approved (Cancer)
NEK9
inhibitor IC50 = 1
| CEP250 inhibitor | ||||
| (with | ||||
| WDB002 | CEP250 | Nsp13 | Clinical Trial | FKBP) |
| Kd = 0.29 | ||||
| PPIA- | ||||
| IMPDH2 | ||||
| modulator | ||||
| Sanglifehrin A153 | IMPDH2 | Nsp14 | Pre-clinical | PPIA KD = |
| 0.2 | ||||
| IDPDH2 | ||||
| Binding |
EC50 =
11.5 (with PPIA)
FK-506
154 FKBP7 Orf8
FKBP10
Approved (Organ rejection)
FKBP
binder
Pevonedistat67 CUL2 Orf10 Clinical Trial
Ternatin 4155 Translation Pre-clinical
NEDD8-
activating enzyme inhibitor IC50 = 4.7
eEF1A
inhibitor IC50 = 71
4E2RCat
58 Translation Pre-clinical
eIF4E/G PPI
inhibitor IC50 = 13500
Tomivosertib156,157 Translation Clinical Trial
MNK1/2
inhibitor IC50 = 2.4
Viral
158
Pre-clinical
Cyclophilin inhibitor
Compound 2
Transcription
KD = 24
Compound 10159 Viral
Transcription
PS306130 ER protein
processing
Pre-clinical
Pre-clinical
PI4K-IIIβ
inhibitor IC50 = 3.4
Sec61 inhibitor IC50 = 20-
500
IHVR-19029160,161
ER protein Clinical Trial processing
Antiviral activity
IC50 = 1200
Captopril
162
Cell Entry
Approved (Hypertension)
ACE
inhibitor Ki = 3
Lisinopril163
Cell Entry
Approved (Hypertension)
ACE
inhibitor Ki = 0.27
Camostat164,165 Cell Entry Approved (Pancreatitis)
Nafamostat164,166 Cell Entry Approved (Anticoagulant)
Serine protease 1 inhibitor IC50 < 1000
Serine protease 1 inhibitor IC50 = 100
Chloram-
phenicol167 Mitochondrial
ribosome
Approved (Bacterial infection)
Mito- chondrial ribosome inhibitor IC50 = 7400
Tigecycline168 Mitochondrial
ribosome
Approved (Bacterial infection)
Mito- chondrial ribosome inhibitor IC50 = 3300
Linezolid169
Mitochondrial ribosome
Approved (Bacterial infection)
Mito- chondrial ribosome inhibitor IC50 = 16000
a. These molecules derive from expert analysis of human protein interactors of SARS-Co-V2 and reagents and drugs that modulate them; not readily available from the chemoinformatically-searchable literature.
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