Table 1.
Antiviral compounds acting against filovirus entry.
| Category | Target | Drug activity | Molecules | References |
|---|---|---|---|---|
| Broad spectrum molecules | Attachment | Mannose-specific lectins | griffithsin, concanavalin A, cyanovirin N | (Balzarini et al., 2004;Barton et al., 2014) |
| Endosomal processing | Protease inhibitors | Cys&Ser protease inhibitors (leupeptin) | (Chandran et al., 2005;Schornberg et al., 2006;Barrientos et al., 2007;Shah et al., 2010;Gnirss et al., 2012;Elshabrawy et al., 2014;Nishimura et al., 2015;Zhou et al., 2015;van der Linden et al., 2016) | |
| Cys protease inhibitors (E-64 and E-64d) | ||||
| catL&catB inhibitors (FY-dmk) | ||||
| catB inhibitors (CA-074, CA-074Me, nafamostat mesilate) | ||||
| catL inhibitors (oxobarzate, ZY(t-Bu)-dmk, triazine derivatives 5705213 and 7402683, and K11777) | ||||
| Endosome disruption | genistein, tyrphostin AG1478, chloroquine | (Savarino et al., 2001;Keyaerts et al., 2004;Keyaerts et al., 2009;Madrid et al., 2013) | ||
| Fusion | Intercaling agents | LJ001, dUY11, arbidol | (St Vincent et al., 2010;Wolf et al., 2010;Pécheur et al., 2016) | |
| Unclear | 25HC oxysterols, teicoplanin | (Liu et al., 2013;Schoggins et al., 2013;Wang et al., 2016) | ||
| Filovirus-specific compounds | Attachment | Lectin competitors | tridecafullerenes | (Muñoz et al., 2016) |
| Fusion | NPC1 inhibitors | U18666A, imipramine, Ro48-8071, compounds 3.47 and 3.0, and MBX2254 and MBX2270 | (Cenedella, 2009;Côté et al., 2011; Kolokoltsov et al., 2012; Miller et al., 2012;Lee et al., 2013;Shoemaker et al., 2013;Basu et al., 2015) | |
| GP2 inhibitors | compound 7 | (Basu et al., 2011) | ||
| Approved drugs against other targets | Attachment | Glycosaminoglycan competitor | heparin | (Salvador et al., 2013;Cheng et al., 2015;O'Hearn et al., 2015) |
| Uptake | Cytoskeleton inhibitors | vinblastine, vincristine, colchicine, nocodazole, cytochalasin B and D, latrunculin A, chondramides | (Kouznetsova et al., 2014;Beck et al., 2016) | |
| Endosomal processing | G protein-coupled receptor antagonsits | benztropine mesylate | (Cheng et al., 2015) | |
| Endosomal pH increase | omeprazol, esomeprazol | (Long et al., 2015) | ||
| Unclear | Estrogen receptor modulators | clomiphene, toremiphene, raloxifene, taxomifene | (Johansen et al., 2013;Shoemaker et al., 2013;Gehring et al., 2014;Kouznetsova et al., 2014;Sakurai et al., 2015;Zhao et al., 2016;Beck et al., 2016) | |
| Ion channel inhibitors | amiodarone, dronedarone, verapamil, tetrandine, nimodipine, diltiazem, digoxin, rottlerin, noricumazole A) |
In addition to serological and peptide-based approaches, numerous studies report potential small anti-filovirus molecules. These compounds can be sorted in three categories (broad-spectrum molecules, filovirus-specific compounds and repurposed FDA-approved therapeutics). In each category, molecules have been arranged according to their targeted entry process and then following their specific activity when described.