Ion Channels as Therapeutic Targets for Viral Infections: Further Discoveries and Future Perspectives

Yu, 2005, Overview of molecular relationships in the voltage-gated ion channel superfamily, Pharmacol. Rev., 57, 387, 10.1124/pr.57.4.13

Hanna, 2006, Genetic neurological channelopathies, Nat. Clin. Pract. Neurol., 2, 252, 10.1038/ncpneuro0178

Netter, 2004, Heptad repeat 2-based peptides inhibit avian sarcoma and leukosis virus subgroup a infection and identify a fusion intermediate, J. Virol., 78, 13430, 10.1128/JVI.78.24.13430-13439.2004

Verkman, 2008, Chloride channels as drug targets, Nat. Rev. Drug Discov., 8, 153, 10.1038/nrd2780

Phillips, 2018, Skeletal muscle channelopathies, Neurotherapeutics, 15, 954, 10.1007/s13311-018-00678-0

Kim, 2014, Channelopathies, Korean J. Pediatrics, 57, 1, 10.3345/kjp.2014.57.1.1

Garcia-Elias, A., and Benito, B. (2018). Ion channel disorders and sudden cardiac death. Int. J. Mol. Sci., 19.

Vaeth, 2018, Ion channelopathies of the immune system, Curr. Opin. Immunol., 52, 39, 10.1016/j.coi.2018.03.021

Farre, 2014, New strategies in ion channel screening for drug discovery: Are there ways to improve its productivity?, Expert Opin. Drug Discov., 9, 1103, 10.1517/17460441.2014.942217

McManus, 2014, HTS assays for developing the molecular pharmacology of ion channels, Curr. Opin. Pharmacol., 15, 91, 10.1016/j.coph.2014.01.004

Nieva, 2012, Viroporins: Structure and biological functions, Nat. Rev. Genet., 10, 563, 10.1038/nrmicro2820

Nieva, 2015, Viroporins: Structures and functions beyond cell membrane permeabilization, Viruses, 7, 5169, 10.3390/v7102866

Royle, 2015, Emerging roles of viroporins encoded by DNA viruses: Novel targets for antivirals?, Viruses, 7, 5375, 10.3390/v7102880

Hover, 2017, Viral dependence on cellular ion channels—An emerging antiviral target?, J. Gen. Virol., 98, 345, 10.1099/jgv.0.000712

Helenius, 1980, On the entry of semliki forest virus into BHK-21 cells, J. Cell Biol., 84, 404, 10.1083/jcb.84.2.404

Wattiaux, 1966, Functions of lysosomes, Annu. Rev. Physiol., 28, 435, 10.1146/annurev.ph.28.030166.002251

Scott, 2010, Ion flux and the function of endosomes and lysosomes: PH is just the start, BioEssays, 33, 103, 10.1002/bies.201000108

Pamarthy, 2018, The curious case of vacuolar ATPase: Regulation of signaling pathways, Mol. Cancer, 17, 1, 10.1186/s12943-018-0811-3

Stauber, 2010, Sorting motifs of the endosomal/lysosomal CLC chloride transporters, J. Biol. Chem. J. Biol. Chem., 285, 34537, 10.1074/jbc.M110.162545

Scheel, 2005, Voltage-dependent electrogenic chloride/proton exchange by endosomal CLC proteins, Nature, 436, 424, 10.1038/nature03860

Steinberg, 2010, A cation counterflux supports lysosomal acidification, J. Cell Biol., 189, 1171, 10.1083/jcb.200911083

Brett, 2005, The yeast endosomal Na+(K+)/H+ exchanger Nhx1 regulates cellular pH to control vesicle trafficking, Mol. Biol. Cell, 16, 1396, 10.1091/mbc.e04-11-0999

Huynh, 2007, Regulation of vacuolar PH and its modulation by some microbial species, Microbiol. Mol. Biol. Rev., 71, 452, 10.1128/MMBR.00003-07

2005, Na+/H+ exchange modulates acidification of early rat liver endocytic vesicles, Am. J. Physiol. Cell Physiol., 269, C943

Fuchs, 1989, A possible role for Na+,K+-ATPase in regulating ATP-dependent endosome acidification, Proc. Natl. Acad. Sci. USA, 86, 539, 10.1073/pnas.86.2.539

Luzio, 2007, The role of calcium and other ions in sorting and delivery in the late endocytic pathway, Biochem. Soc. Trans., 35, 1088, 10.1042/BST0351088

Gerasimenko, 1998, Calcium uptake via endocytosis with rapid release from acidifying endosomes, Curr. Biol., 8, 1335, 10.1016/S0960-9822(07)00565-9

Hover, S., Foster, B., Fontana, J., Kohl, A., Goldstein, S.A., Barr, J.N., and Mankouri, J. (2018). Bunyavirus requirement for endosomal K+ reveals new roles of cellular ion channels during infection. PLoS Pathog., 14.

Staring, J., Raaben, M., and Brummelkamp, T.R. (2018). Viral escape from endosomes and host detection at a glance. J. Cell Sci., 131.

Fujioka, 2018, A sialylated voltage-dependent Ca2+ channel binds hemagglutinin and mediates influenza a virus entry into mammalian cells, Cell Host Microbe, 23, 809, 10.1016/j.chom.2018.04.015

Stauffer, 2014, Stepwise priming by acidic pH and a high K+ concentration is required for efficient uncoating of influenza a virus cores after penetration, J. Virol., 88, 13029, 10.1128/JVI.01430-14

Simmons, 2015, Ebolavirus glycoprotein directs fusion through NPC1+ endolysosomes, J. Virol., 90, 605, 10.1128/JVI.01828-15

Penny, C.J., Vassileva, K., Jha, A., Yuan, Y., Chee, X., Yates, E., Mazzon, M., Kilpatrick, B.S., Muallem, S., and Marsh, M. (2018). Mining of Ebola virus entry inhibitors identifies approved drugs as two-pore channel pore blockers. Biochim. Biophys. Acta Mol. Cell Res.

Gunaratne, 2018, NAADP-dependent Ca2+ signaling regulates Middle East respiratory syndrome-Coronavirus pseudovirus translocation through the endolysosomal system, Cell Calcium, 75, 30, 10.1016/j.ceca.2018.08.003

Li, 2019, Calcium channel blockers reduce severe fever with thrombocytopenia syndrome virus (SFTSV) related fatality, Cell Res., 29, 739, 10.1038/s41422-019-0214-z

Ou, 2020, Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV, Nat. Commun., 11, 1, 10.1038/s41467-020-15562-9

Hover, 2016, Modulation of potassium channels inhibits bunyavirus infection, J. Biol. Chem., 291, 3411, 10.1074/jbc.M115.692673

Punch, 2018, Potassium is a trigger for conformational change in the fusion spike of an enveloped RNA virus, J. Biol. Chem., 293, 9937, 10.1074/jbc.RA118.002494

Charlton, 2019, Cellular cholesterol abundance regulates potassium accumulation within endosomes and is an important determinant in bunyavirus entry, J. Biol. Chem., 294, 7335, 10.1074/jbc.RA119.007618

Dubey, 2019, G protein-coupled and ATP-sensitive inwardly rectifying potassium ion channels are essential for HIV entry, Sci. Rep., 9, 1, 10.1038/s41598-019-40968-x

Dobson, S.J., Mankouri, J., and Whitehouse, A. (2020). Identification of potassium and calcium channel inhibitors as modulators of polyomavirus endosomal trafficking. Antiviral Res., 104819.

Panou, 2020, Glibenclamide inhibits BK polyomavirus infection in kidney cells through CFTR blockade, Antiviral Res., 178, 104778, 10.1016/j.antiviral.2020.104778

Das, D.K., Bulow, U., Diehl, W.E., Durham, N.D., Senjobe, F., Chandran, K., Luban, J., and Munro, J.B. (2020). Conformational changes in the Ebola virus membrane fusion machine induced by pH, Ca2+, and receptor binding. PLoS Biol., 18.

Zumla, 2015, Middle east respiratory syndrome, Lancet, 386, 995, 10.1016/S0140-6736(15)60454-8

Park, 2016, Proteolytic processing of middle east respiratory syndrome coronavirus spikes expands virus tropism, Proc. Natl. Acad. Sci. USA, 113, 12262, 10.1073/pnas.1608147113

Mille, 2014, Host cell entry of Middle East respiratory syndrome coronavirus after two-step, furin-mediated activation of the spike protein, Proc. Natl. Acad. Sci. USA, 111, 15214, 10.1073/pnas.1407087111

Ruas, 2010, Purified TPC isoforms form NAADP receptors with distinct roles for Ca2+ signaling and endolysosomal trafficking, Curr. Biol., 20, 703, 10.1016/j.cub.2010.02.049

Huang, 2020, Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China, Lancet, 395, 497, 10.1016/S0140-6736(20)30183-5

Zhu, 2020, A novel coronavirus from patients with pneumonia in China, 2019, N. Engl. J. Med., 382, 727, 10.1056/NEJMoa2001017

Li, 2018, Epidemiological and clinical features of laboratory-diagnosed severe fever with thrombocytopenia syndrome in China, 2011–17: A prospective observational study, Lancet Infect. Dis., 18, 1127, 10.1016/S1473-3099(18)30293-7

Bao, 2011, A family cluster of infections by a newly recognized bunyavirus in Eastern China, 2007: Further evidence of person-to-person transmission, Clin. Infect. Dis., 53, 1208, 10.1093/cid/cir732

Khan, N., Lakpa, K.L., Halcrow, P.W., Afghah, Z., Miller, N.M., Geiger, J.D., and Chen, X. (2019). BK channels regulate extracellular Tat-mediated HIV-1 LTR transactivation. Sci. Rep., 9.

Cao, 2015, BK channels alleviate lysosomal storage diseases by providing positive feedback regulation of lysosomal Ca2+ release, Dev. Cell, 33, 427, 10.1016/j.devcel.2015.04.010

Sakurai, 2015, Two-pore channels control Ebola virus host cell entry and are drug targets for disease treatment, Science, 347, 995, 10.1126/science.1258758

Kawano, 2009, Calcium bridge triggers capsid disassembly in the cell entry process of simian virus 40, J. Biol. Chem., 284, 34703, 10.1074/jbc.M109.015107

Bradbury, 1999, Intracellular CFTR: Localization and function, Physiol. Rev., 79, S175, 10.1152/physrev.1999.79.1.S175

Collaco, 2013, Functional vacuolar ATPase (V-ATPase) proton pumps traffic to the enterocyte brush border membrane and require CFTR, Am. J. Physiol. Cell Physiol., 305, C981, 10.1152/ajpcell.00067.2013

Wang, S., Liu, Y., Guo, J., Wang, P., Zhang, L., Xiao, G., and Wang, W. (2017). Screening of FDA-approved drugs for inhibitors of Japanese Encephalitis virus infection. J. Virol., 91.

Dionicio, 2018, Dengue virus induced changes in Ca2+ homeostasis in human hepatic cells that favor the viral replicative cycle, Virus Res., 245, 17, 10.1016/j.virusres.2017.11.029

Jungfleisch, 2018, The TRPV4 channel links calcium influx to DDX3X activity and viral infectivity, Nat. Commun., 9, 2307, 10.1038/s41467-018-04776-7

Bouchard, 2001, Calcium signaling by HBx protein in hepatitis B virus DNA replication, Science, 294, 2376, 10.1126/science.294.5550.2376

Yao, 2018, Hepatitis B virus X protein upregulates intracellular calcium signaling by binding C-terminal of orail protein, Curr. Med Sci., 38, 26, 10.1007/s11596-018-1843-z

Chakraborty, 2017, The epsilon motif of hepatitis B virus RNA exhibits a potassium-dependent ribonucleolytic activity, FEBS J., 284, 1184, 10.1111/febs.14050

Han, 2017, Voltage-dependent anion channel 1 interacts with ribonucleoprotein complexes to enhance infectious bursal disease virus polymerase activity, J. Virol., 91, e00584-17, 10.1128/JVI.00584-17

Müller, M., Slivinski, N., Todd, E.J., Khalid, H., Li, R., Karwatka, M., Merits, A., Mankouri, J., and Tuplin, A. (2019). Chikungunya virus requires cellular chloride channels for efficient genome replication. PLoS Negl. Trop. Dis., 13.

Costa, V.V., Del Sarto, J.L., Rocha, R.F., Silva, F.R., Doria, J.G., Olmo, I.G., Marques, R.E., Queiroz-Junior, C.M., Foureaux, G., and Araújo, J.M.S. (2017). N-methyl-D-aspartate (NMDA) receptor blockade prevents neuronal death induced by Zika virus infection. MBio, 8.

Sirohi, 2017, Can an FDA-approved Alzheimer’s drug be repurposed for alleviating neuronal symptoms of zika virus?, mBio, 8, e00916-17, 10.1128/mBio.00916-17

Zhang, 2019, Regulation of T-type Ca2+ channel expression by interleukin-6 in sensory-like ND7/23 cells post-herpes simplex virus (HSV-1) infection, J. Neurochem., 151, 238, 10.1111/jnc.14697

Zhang, 2017, Regulation of T-type Ca2+ channel expression by herpes simplex virus-1 infection in sensory-like ND7 cells, J. Neurovirol., 23, 657, 10.1007/s13365-017-0545-9

Chang-Graham, A.L., Perry, J.L., Strtak, A.C., Ramachandran, N.K., Criglar, J.M., Philip, A.A., Patton, J.T., Estes, M.K., and Hyser, J.M. (2019). Rotavirus calcium dysregulation manifests as dynamic calcium signaling in the cytoplasm and endoplasmic reticulum. Sci. Rep., 9.

Suzuki, 2014, Imaging intraorganellar Ca2+ at subcellular resolution using CEPIA, Nat. Commun., 5, 4153, 10.1038/ncomms5153

Perry, 2015, Use of genetically-encoded calcium indicators for live cell calcium imaging and localization in virus-infected cells, Methods, 90, 28, 10.1016/j.ymeth.2015.09.004

Zhang, 2000, A functional NSP4 enterotoxin peptide secreted from rotavirus-infected cells, J. Virol., 74, 11663, 10.1128/JVI.74.24.11663-11670.2000

Jiang, 2016, Shikonin inhibits intestinal calcium-activated chloride channels and prevents rotaviral diarrhea, Front. Pharmacol., 7, 270, 10.3389/fphar.2016.00270

Zhang, Q., Chen, F., Martin-Caraballo, M., and Hsia, S. (2019). Modulation of voltage-gated sodium channel (VGSC) activity in human dorsal root ganglion (DRG) neurons by herpesvirus quiescent infection. J. Virol., 714691.

Peischard, 2019, A kidnapping story: How coxsackievirus B3 and its host cell interact, Cell. Physiol. Biochem., 53, 121, 10.33594/000000125

Omar, S., Clarke, R., Abdullah, H., Brady, C., Corry, J., Winter, H., Touzelet, O., Power, U.F., Lundy, F., and McGarvey, L.P. (2017). Respiratory virus infection up-regulates TRPV1, TRPA1 and ASICS3 receptors on airway cells. PLoS ONE, 12.

Brand, J.D., Lazrak, A., Trombley, J.E., Shei, R.J., Adewale, A.T., Tipper, J.L., Yu, Z., Ashtekar, A.R., Rowe, S.M., and Matalon, S. (2018). Influenza-mediated reduction of lung epithelial ion channel activity leads to dysregulated pulmonary fluid homeostasis. JCI Insight, 3.

Nwogu, 2018, The cellular chloride channels CLIC1 and CLIC4 contribute to virus-mediated cell motility, J. Biol. Chem., 293, 4582, 10.1074/jbc.RA117.001343

Seebohm, 2008, Long QT syndrome—Associated mutations in KCNQ1 and KCNE1 subunits disrupt normal endosomal recycling of IKs channels, Circ. Res., 103, 1451, 10.1161/CIRCRESAHA.108.177360

Chen, 2009, Inhibition of Na+ transport in lung epithelial cells by respiratory syncytial virus infection, Am. J. Respir. Cell Mol. Biol., 40, 588, 10.1165/rcmb.2008-0034OC

Kaskinen, A., Alexandersson, A., Andersson, S., Saxén, H., Peltola, V., Kolho, K.L., and Helve, O. (2020). Decreased airway epithelial ion transport was associated with the severity of the respiratory syncytial virus infection and complications in infants. Acta Paediatr., 15311.

Crambert, G., Ernandez, T., Lamouroux, C., Roth, I., Dizin, E., Martin, P.Y., Féraille, E., and Hasler, U. (2014). Epithelial sodium channel abundance is decreased by an unfolded protein response induced by hyperosmolality. Physiol. Rep., 2.

Kennedy, P.G., Montague, P., Scott, F., Grinfeld, E., Ashrafi, G.H., Breuer, J., and Rowan, E.G. (2013). Varicella-zoster viruses associated with post-herpetic neuralgia induce sodium current density increases in the ND7-23 Nav-1.8 Neuroblastoma cell line. PLoS ONE, 8.

Tang, 2015, Primary erythromelalgia: A review, Orphanet J. Rare Dis., 10, 127, 10.1186/s13023-015-0347-1

Knight, 2015, Merkel cell polyomavirus small T antigen mediates microtubule destabilization to promote cell motility and migration, J. Virol., 89, 35, 10.1128/JVI.02317-14

Peretti, 2015, Chloride channels in cancer: Focus on chloride intracellular channel 1 and 4 (CLIC1 AND CLIC4) proteins in tumor development and as novel therapeutic targets, Biochim. Biophys. Acta Biomembr., 1848, 2523, 10.1016/j.bbamem.2014.12.012