Abstract
With the advent of ivermectin, tremendous improvement in public health has been observed, especially in the treatment of onchocerciasis and lymphatic filariasis that created chaos mostly in rural, sub-Saharan Africa and Latin American countries. The discovery of ivermectin became a boon to millions of people that had suffered in the pandemic and still holds its pharmacological potential. Ivermectin continued to surprise scientists because of its notable role in the treatment of various other tropical diseases (Chagas, leishmaniasis, worm infections, etc.) and is viewed as the safest drug with the least toxic effects. The current review highlights its role in unexplored avenues towards forging ahead of the repositioning of this multitargeted drug in cancer, viral (the evaluation of the efficacy of ivermectin against SARS-Cov-2 is under investigation) and bacterial infection and malaria. This article also provides a glimpse of regulatory considerations of drug repurposing and current formulation strategies. Due to its broad-spectrum activity, multitargeted nature and promising efforts are put towards the repurposing of this drug throughout the field of medicine. This single drug originated from a microbe, changed the face of global health by proving its unmatched success and progressive efforts continue in maintaining its bequestnin the management of global health by decreasing the burden of various diseases worldwide.
Keywords: Ivermectin, tropical diseases, multitargeted nature, drug repurposing, global health, SARS-CoV-2
Graphical Abstract
[http://dx.doi.org/10.2174/1381612033455279] [PMID: 12678873]
[http://dx.doi.org/10.1038/nrmicro1048] [PMID: 15550944]
[http://dx.doi.org/10.1128/AAC.15.3.361] [PMID: 464561]
[http://dx.doi.org/10.1016/j.ijantimicag.2007.08.023] [PMID: 18037274]
[http://dx.doi.org/10.2183/pjab.87.13] [PMID: 21321478]
[http://dx.doi.org/10.1186/1756-3305-5-28] [PMID: 22313631]
[http://dx.doi.org/10.1093/cid/cix1069] [PMID: 29360939]
[PMID: 12640474]
[http://dx.doi.org/10.1371/journal.pntd.0006825] [PMID: 30252856]
[http://dx.doi.org/10.1016/j.pt.2017.02.004] [PMID: 28285851]
[http://dx.doi.org/10.1016/S0190-9622(00)90131-2] [PMID: 10642678]
[http://dx.doi.org/10.1016/j.jpba.2005.08.026] [PMID: 16242280]
[http://dx.doi.org/10.1208/s12248-007-9000-9] [PMID: 18446504]
[http://dx.doi.org/10.1186/s12936-017-1801-4] [PMID: 28434401]
[http://dx.doi.org/10.1016/j.ijpddr.2011.10.001] [PMID: 24533264]
[PMID: 26954318]
[http://dx.doi.org/10.2165/00003495-199142040-00007] [PMID: 1723366]
[http://dx.doi.org/10.1097/QCO.0b013e328010774c] [PMID: 17075336]
[http://dx.doi.org/10.1016/S0140-6736(89)90136-0] [PMID: 2567440]
[http://dx.doi.org/10.1056/NEJMc1917344] [PMID: 32813957]
[http://dx.doi.org/10.1016/j.ijpharm.2002.12.002] [PMID: 15158963]
[http://dx.doi.org/10.1179/000349802125000826] [PMID: 12061975]
[http://dx.doi.org/10.4103/0974-777X.81692] [PMID: 21731302]
[http://dx.doi.org/10.1186/1475-2883-2-S1-S5] [PMID: 14975062]
[http://dx.doi.org/10.1016/S1473-3099(16)30544-8] [PMID: 28012944]
[http://dx.doi.org/10.1093/cid/civ882] [PMID: 26486704]
[http://dx.doi.org/10.1111/j.1365-3024.2005.00792.x] [PMID: 16179035]
[http://dx.doi.org/10.1086/599090] [PMID: 19456233]
[http://dx.doi.org/10.4103/2229-5070.138544] [PMID: 25250237]
[http://dx.doi.org/10.4269/ajtmh.2009.80.956] [PMID: 19478258]
[http://dx.doi.org/10.1016/S0065-308X(05)60004-8] [PMID: 16230105]
[http://dx.doi.org/10.1017/S0031182005008218] [PMID: 16569295]
[http://dx.doi.org/10.1016/S0140-6736(10)60586-7] [PMID: 20739055]
[http://dx.doi.org/10.1179/000349803235001697] [PMID: 12803872]
[http://dx.doi.org/10.1016/j.pt.2010.02.010] [PMID: 20304707]
[http://dx.doi.org/10.1111/j.1365-3024.2011.01286.x] [PMID: 21366624]
[http://dx.doi.org/10.1371/journal.pmed.0050055] [PMID: 18303943]
[http://dx.doi.org/10.1016/S0140-6736(09)60829-1] [PMID: 19833383]
[http://dx.doi.org/10.1172/JCI200421052] [PMID: 14966556]
[http://dx.doi.org/10.1016/0035-9203(95)90673-8] [PMID: 7747321]
[http://dx.doi.org/10.1186/s13071-019-3370-6] [PMID: 30898141]
[PMID: 23135008]
[http://dx.doi.org/10.1590/S0074-02762005000800002] [PMID: 16444412]
[http://dx.doi.org/10.1016/j.prevetmed.2020.105104] [PMID: 32759025]
[http://dx.doi.org/10.1016/j.cimid.2004.03.004] [PMID: 15225981]
[http://dx.doi.org/10.1128/CMR.19.1.111-126.2006] [PMID: 16418526]
[http://dx.doi.org/10.1242/jcs.185595] [PMID: 27358479]
[http://dx.doi.org/10.1016/j.exppara.2020.108059] [PMID: 33338468]
[http://dx.doi.org/10.4155/tde-2020-0090] [PMID: 33198601]
[http://dx.doi.org/10.1089/vbz.2009.0030] [PMID: 20518644]
[PMID: 9617057]
[http://dx.doi.org/10.1111/j.1948-7134.2011.00122.x] [PMID: 21366765]
[http://dx.doi.org/10.1111/tmi.12870] [PMID: 28326655]
[http://dx.doi.org/10.1016/0022-2011(88)90146-2] [PMID: 3183416]
[http://dx.doi.org/10.1371/journal.pone.0027119] [PMID: 22069494]
[http://dx.doi.org/10.4269/ajtmh.1994.51.83] [PMID: 8059919]
[http://dx.doi.org/10.1016/j.molbiopara.2018.12.005] [PMID: 30658180]
[http://dx.doi.org/10.1186/s13071-019-3599-0] [PMID: 31300011]
[http://dx.doi.org/10.1016/j.jemermed.2013.05.014] [PMID: 23871326]
[http://dx.doi.org/10.1590/S0103-64402004000100015] [PMID: 15322651]
[http://dx.doi.org/10.1159/000495290] [PMID: 30544123]
[http://dx.doi.org/10.1177/1203475420960446] [PMID: 32998532]
[http://dx.doi.org/10.4269/ajtmh.20-1334] [PMID: 33657012]
[http://dx.doi.org/10.1111/tid.13077] [PMID: 30873722]
[http://dx.doi.org/10.1086/313942] [PMID: 10987711]
[PMID: 12953933]
[http://dx.doi.org/10.1086/313787] [PMID: 10816151]
[http://dx.doi.org/10.1007/978-1-4471-6765-5_87]
[http://dx.doi.org/10.1007/s40475-021-00239-0]
[http://dx.doi.org/10.1111/dth.12845] [PMID: 30693620]
[http://dx.doi.org/10.1158/1078-0432.CCR-10-2467] [PMID: 21346147]
[http://dx.doi.org/10.18632/oncotarget.13188] [PMID: 27835600]
[http://dx.doi.org/10.18632/oncotarget.22587] [PMID: 29296196]
[PMID: 22491145]
[http://dx.doi.org/10.1080/15548627.2020.1731266] [PMID: 32186433]
[http://dx.doi.org/10.1080/15548627.2016.1231494] [PMID: 27657889]
[http://dx.doi.org/10.1016/j.bbamcr.2020.118688] [PMID: 32087180]
[http://dx.doi.org/10.1021/acs.jafc.6b02812] [PMID: 27551889]
[http://dx.doi.org/10.1371/journal.pone.0002599] [PMID: 18612415]
[http://dx.doi.org/10.1038/srep16222] [PMID: 26552848]
[http://dx.doi.org/10.1158/0008-5472.CAN-15-2887] [PMID: 27302166]
[http://dx.doi.org/10.1038/nrc3419] [PMID: 23258168]
[http://dx.doi.org/10.15252/emmm.201404084] [PMID: 25143352]
[http://dx.doi.org/10.1093/brain/awv167] [PMID: 26121981]
[http://dx.doi.org/10.2147/DDDT.S237393] [PMID: 32021111]
[http://dx.doi.org/10.1016/j.bbrc.2016.10.064] [PMID: 27771251]
[http://dx.doi.org/10.1016/S1473-3099(04)01043-6] [PMID: 15172341]
[http://dx.doi.org/10.1002/14651858.CD012736.pub2]
[http://dx.doi.org/10.1002/14651858.CD013117] [PMID: 34184757]
[http://dx.doi.org/10.1242/jeb.118570] [PMID: 25994631]
[http://dx.doi.org/10.1074/jbc.R112.406280] [PMID: 23038250]
[http://dx.doi.org/10.1016/S0140-6736(18)32613-8] [PMID: 30878223]
[http://dx.doi.org/10.1002/cpt.1716] [PMID: 31697848]
[http://dx.doi.org/10.1186/1475-2875-13-417] [PMID: 25363349]
[http://dx.doi.org/10.1186/s13071-015-0735-3] [PMID: 25885477]
[http://dx.doi.org/10.4269/ajtmh.2011.11-0160] [PMID: 21734116]
[PMID: 28442746]
[http://dx.doi.org/10.1093/jac/dks147] [PMID: 22535622]
[http://dx.doi.org/10.1016/j.diagmicrobio.2019.03.012] [PMID: 31097261]
[http://dx.doi.org/10.1007/s00705-015-2653-2] [PMID: 26518309]
[http://dx.doi.org/10.1016/j.antiviral.2013.10.004] [PMID: 24161512]
[http://dx.doi.org/10.1016/j.antiviral.2015.12.012] [PMID: 26752081]
[http://dx.doi.org/10.1371/journal.pntd.0006934] [PMID: 30452439]
[http://dx.doi.org/10.1093/cid/ciaa1341]
[http://dx.doi.org/10.1042/BJ20120150] [PMID: 22417684]
[http://dx.doi.org/10.1515/hsz-2015-0171] [PMID: 26351913]
[PMID: 32779815]
[http://dx.doi.org/10.1016/j.antiviral.2020.104787] [PMID: 32251768]
[http://dx.doi.org/10.1128/AAC.01696-12] [PMID: 23165468]
[http://dx.doi.org/10.1371/journal.pntd.0003549] [PMID: 25742173]
[http://dx.doi.org/10.1093/jac/dkt089] [PMID: 23587653]
[http://dx.doi.org/10.1016/j.amepre.2011.06.045] [PMID: 22011424]
[http://dx.doi.org/10.1016/j.bcp.2007.08.005] [PMID: 17880925]
[http://dx.doi.org/10.1016/j.neuron.2012.09.024] [PMID: 23040806]
[http://dx.doi.org/10.1085/jgp.200910336] [PMID: 20231374]
[http://dx.doi.org/10.1085/jgp.200308986] [PMID: 14769846]
[http://dx.doi.org/10.1124/jpet.110.167908] [PMID: 20543096]
[http://dx.doi.org/10.1007/s11064-014-1271-9] [PMID: 24671605]
[http://dx.doi.org/10.1097/WNR.0000000000000211] [PMID: 25004078]
[http://dx.doi.org/10.1007/s00213-018-4869-9] [PMID: 29500584]
[http://dx.doi.org/10.3390/molecules26061791] [PMID: 33810134]
[http://dx.doi.org/10.4103/2230-973X.114897] [PMID: 24015378]
[http://dx.doi.org/10.1016/j.alcohol.2015.03.006] [PMID: 26095588]
[http://dx.doi.org/10.1136/openhrt-2020-001350] [PMID: 32895293]
[http://dx.doi.org/10.1007/s43440-020-00195-y] [PMID: 33389725]
[http://dx.doi.org/10.1007/s00011-011-0307-8] [PMID: 21279416]
[http://dx.doi.org/10.1016/j.ijantimicag.2019.05.003] [PMID: 31071469]
[http://dx.doi.org/10.1080/10837450.2016.1200078] [PMID: 27346432]
[http://dx.doi.org/10.1007/s40262-015-0242-x] [PMID: 25666353]
[http://dx.doi.org/10.1007/s00436-013-3696-5] [PMID: 24366812]
[http://dx.doi.org/10.1155/2016/8043983]
[http://dx.doi.org/10.1186/s13071-019-3719-x] [PMID: 31601244]
[http://dx.doi.org/10.1007/s00436-017-5510-2] [PMID: 28523490]
[http://dx.doi.org/10.1007/s40257-015-0150-8] [PMID: 26254001]
[http://dx.doi.org/10.1016/j.colsurfb.2020.110823] [PMID: 32036331]
[http://dx.doi.org/10.1080/21691401.2017.1307207] [PMID: 28368657]