TABLE 2.
Host-directed antiviral agents under preclinical developmenta
| Host factor function | Antiviral agent(s) | Virus(es) | Host target | Reference(s) |
|---|---|---|---|---|
| Support viral entry | DAS181 | IAV, PIV | Sialic acid receptor | 405–411 |
| R448, cabozantinib | ZIKV | AXL kinase | 412, 413 | |
| Ezetimibe | HCV | NPC1L1 | 166 | |
| Obatoclax, chloroquine, bafilomycin A1, ammonium chloride, Arbidol (umifenovir), chlorpromazine, niclosamide, mefloquine HCl | ZIKV, FLV hRhV, IAV | Regulation of endosomal pH | 413–417 | |
| Glycyrrhizin | IAV | Regulation of endocytotic uptake | 418 | |
| Concanamycin, saliphenylhalamide | IAV | Cellular vacuolar ATPases | 419, 420 | |
| Daptomycin | ZIKV | Modulation of late endosomal function | 417 | |
| LJ001 | IAV, poxvirus, FLV, HIV-1 | Modulation of membrane fluidity | 421 | |
| Thapsigargin | PPRV, NDV | SERCA | 39 | |
| Dynasore | HSV-1 | Dynamin | 422 | |
| MLS000394177, MLS000733230, MLS000730532 | EBOV | Macropinocytic uptake | 423 | |
| Bisindolylmaleimide I, calphostin C, chelerythrine, enzastaurin, staurosporine | WNV, IAV | PKC | 424, 425 | |
| Fattiviracin | HIV-1 | Internalization factors | 426 | |
| Aprotinin, camostat | IAV | Protease inhibitor | 427, 428 | |
| Jasplakinolide, cytochalasin D | hAdV | Actin polymerization | 429 | |
| Amiloride (EIPA) | CVB3, hAdV | Sodium-proton exchange | 430 | |
| Emetine, cephaeline | PPRV, NDV, BPXV, BHV-1, ZIKV, EBOV | Lysosomal function | 431, 432 | |
| Tenovin-1 | ZIKV | SirT1 and SirT2 | 433 | |
| Clonidine | IAV | α2-Adrenergic receptors | 434 | |
| Nanchangmycin | ZIKV | AXL kinase | 433 | |
| Erlotinib | HCV | EGFR and GAK | 104, 165 | |
| Sunitinib | HCV | AAK1 | 104 | |
| NIM-811, Debio-025 | EV | Cyclophilin | 435 | |
| STI-571, Gleevec, imatinib, nilotinib, dasatinib | Poxvirus, PyV, HIV-1 | Abl family protein kinases | 436, 437 | |
| Support viral genome replication, transcription, and translation | SD-29 | HSV-1 | RACK1 | 438 |
| Torin1, rapamycin | CMV, BEFV | mTOR kinase | 439–441 | |
| Hippuristanol, silvestrol | CMV, ZIKV | eIF4A | 440, 442 | |
| CGP57380 | HSV-1, poxvirus, hCMV | MNK1 | 38, 443–445 | |
| 4E2RCat, 4EGI-1 | CoV, BPXV | eIF4E/eIF4G interaction | 38, 446 | |
| Apigenin | FMDV, EV71 | hnRNP A1 and A2 | 447, 448 | |
| AG879 | IAV, SV, HSV-1, MHV, RV | NGFR | 121, 129 | |
| Genistein | HIV-1 | Tyrosine kinase | 449 | |
| Tyrphostin A9 | IAV, SV, HSV-1, MHV, RV | PDGFR | 121, 129 | |
| Gefitinib (Iressa) | Poxvirus, hCMV | EGFR | 450, 451 | |
| Ivermectin | IAV | Importins | 452 | |
| Verdinexor, DP2392-E10, leptomycin B | IAV | XPO1 | 453–455 | |
| TG100572 | HSV-1 | Src family kinases | 156 | |
| Vemurafenib | IAV | Raf | 456 | |
| U0126, Cl-1040 (PD184352) | IAV, IBV, PEDV, AstV, BDV, CoV, JUNV, HSV-1 | MEK1/2 | 457–464 | |
| FR180204, Ag-126 | VEEV, DENV, lentivirus | ERK1/2 | 465, 466 | |
| SB203580 | EMCV | p38 | 467 | |
| AS601245, SP600125 | IAV, hCMV | JNK | 468, 469 | |
| Mycophenolic acid, ribavirin | ZIKV, IAV, RSV, CoV, EV71, CVB3, HCV | IMPDH | 417, 470–472 | |
| Leflunomide, compound A3 | FLV | DHODH | 368 | |
| TVB-2640 | HCV | FAS | 389, 473 | |
| Statins (atorvastatin, fluvastatin, lovastatin, pravastatin, and simvastatin) | HCV | HMG-CoA reductase | 393 | |
| Clypearin, corilagin, TG003 | IAV | CLK1 | 474 | |
| Silvestrol, pateamine | IAV | eIF4A | 475, 476 | |
| Curcumin, demethoxycurcumin, bisdemethoxycurcumin, EF-24, FLLL32 | JEV, RVFV, HCV, EV71 | Ubiquitin-proteasome, PKC, NF-κB, Akt | 477–480 | |
| PIK93, BF738735, GW5074, T-00127-HEV1 | EV | PI4KB | 481, 482 | |
| Itraconazole, 25-hydroxycholesterol, AN-12-H5, T-00127-HEV2, TTP-8307 | EV | OSBP | 481 | |
| EYP001 | HBV | Synthetic farnesoid X receptor | 483 | |
| APG-1387 | HBV | cIAP2 | 484 | |
| Fenretinide (4-HPR) | ZIKV, DENV | Activator of retinoid receptors | 485 | |
| Difluoromethylornithine, diethylnorspermine | ZIKV, DENV | Host polyamine synthesis | 486 | |
| Cyclopiazonic acid (CPA) | hRSV | Intracellular calcium ATPase | 487 | |
| MK2206 | IAV | Akt | 488 | |
| PD-0332991 | HSV-1 | CDK4/6 | 489 | |
| LDC4297 | hCMV, AdV | CDK7 | 490 | |
| JMN3-003 | Myxovirus | G1-phase arrest | 369 | |
| AGK2 | HBV | SirT2 | 491 | |
| Amiloride (EIPA) | CVB3, hAdV35 | Sodium-proton exchange | 429, 430 | |
| HL05100P2, cyclosporine, NIM-811, CRV431, CMX157 | EAV, PRRSV, HCV, HBV | Cyclophilin | 435, 492, 493 | |
| Emetine | PPRV, NDV, BPXV, BHV-1 | Unknown | 431, 432 | |
| Cephaeline | ZIKV, EBOV | Unknown | 431, 432 | |
| Nitazoxanide, tizoxanide | ZIKV, RV, NV, HBV, HCV, IAV | Unknown | 494 | |
| Glycyrrhizin | CVB3, hAdV, IAV | Unknown | 418, 429, 430 | |
| RG7834 | HBV | Unknown | 495 | |
| Veregen (sinecatechins) | HPV | Unknown | 21 | |
| Support virus assembly and release | Brefeldin A | DENV, HCV | ADP-ribosylation factor | 496, 497 |
| PF4620110, LCQ908 | HCV | DGAT1 | 498 | |
| AG879 | IAV, SINV, HSV-1, MHV, RV | NGFR | 121, 129 | |
| U18666A | IAV | Annexin A6 | 499 | |
| UV-4B | DENV, IAV | ER glycosylation pathway | 500 | |
| Tyrphostin A9 (A9) | IAV, SINV, HSV-1, MHV, RV | PDGFR | 121, 129 | |
| Verapamil, chlorpromazine | IAV, SINV, VSV | Calcium channel blocker | 501, 502 | |
| Gemfibrozil, lovastatin | IAV | Unknown | 503 | |
| Suramin | ZIKV | Glycosylation (secretory pathway) | 504, 505 | |
| Dynasore | HSV | Protein trafficking | 422 | |
| DEBIO-025 | HCV | Cyclophilin A | 506, 507 | |
| Bortezomib | ZIKV | Proteasome function | 417 | |
Abbreviations: AAK1, adaptor-associated protein kinase 1; AdV, adenovirus; AstV, astrovirus; BDV, Borna disease virus; BPXV, buffalopox virus; BHV1, bovine herpesvirus 1; BEFV, bovine ephemeral fever virus; CDK, cyclin-dependent kinase; CVB3, coxsackievirus B3; cIAP2, cellular inhibitor of apoptosis protein 2; CLK1, Cdc2-like kinase 1; CMV, cytomegalovirus; CoV, coronavirus; DGAT1, diacylglycerol acyltransferase-1; DENV, dengue virus; DHODH, dihydroorotate dehydrogenase; EAV, equine arteritis virus; EBOV, Ebola virus; EGFR, epidermal growth factor receptor; EMCV, encephalomyocarditis virus; EV, enterovirus; eIF4E, eukaryotic translation initiation factor 4E; ERK, extracellular-regulated kinase; FLV, flavivirus; FAS, fatty acid synthase; FMDV, foot-and-mouth disease virus; GAK, cyclin G-associated kinase; HBV, hepatitis B virus; HCV, hepatitis C virus; HIV-1, human immunodeficiency virus type 1; HMG-CoA, 3-hydroxy-3-methylglutaryl coenzyme A; hnRNPA1, heterogeneous nuclear ribonucleoprotein A1; hRSV, human Rous sarcoma virus; hCMV, human cytomegalovirus; hAdV, human adenovirus; hRhV, human rhinovirus; HSV-1, herpes simplex virus 1; IAV, influenza A virus; IBV, influenza B virus; IMPDH, IMP dehydrogenase; JEV, Japanese encephalitis virus; JUNV, Junin virus; MHV, mouse hepatitis virus; MNK1, MAPK-interacting kinase 1; NDV, Newcastle disease virus; NGFR, nerve growth factor receptor; NPC1L1, Niemann-Pick C1-like 1; NF-κB, nuclear factor kappa B; OSBP, oxysterol-binding protein; PDGFR, platelet-derived growth factor receptor; PIV, parainfluenza virus; PEDV, porcine epidemic diarrhea virus; PI4KB, phosphatidylinositol 4-kinase IIIβ; PKC, protein kinase C; PPRV, peste des petits ruminants virus; PRRSV, porcine reproductive and respiratory syndrome virus; PyV, polyoma virus; RACK1, receptor for activated C kinase 1; RVFV, Rift Valley fever virus; RSV, Rous sarcoma virus; RV, rotavirus; SERCA, sarco/endoplasmic reticulum Ca2+-ATPase; SV, Sendai virus; SINV, Sindbis virus; SirT1, Sirtuin type 1; VSV, vesicular stomatitis virus; VEEV, Venezuelan equine encephalitis virus; WNV, West Nile virus; XPO1, exportin 1; ZIKV, Zika virus.