Abstract
Sulfur and oxygen containing-compounds are a relevant class of derivatives that is constantly growing due to their wide range of pharmacological activity, including the antiviral one. As proof of this, there are several FDA approved antiviral compounds having sulfur and oxygen in their structures. Among RNA viruses, the flavivirus genus (e.g. Dengue, West Nile, Yellow Fever and Zika viruses) holds a relevant place within zoonotic pathogens and thus flavivirus infections are considered a growing risk for the public health. As a consequence, the drug discovery process aimed at identify new anti- flavivirus agents is of great relevance and will help to find effective therapies not available yet. One of the most alarming features of flaviviruses is their ability to co-infect the host, thus aggravating the symptoms of the disease. Therefore, finding compounds endowed with a broad-spectrum anti-flavivirus activity is now becoming a pressing need. In this review, we describe the most promising compounds having both sulfur and oxygen in their structures characterized by a broad-spectrum activity against different flaviviruses. Furthermore, the synthetic procedures applied for the preparation of the described derivatives are also reported. Readers can be inspired by the contents of this review to design and synthesize more effective anti-flavivirus agents as well as to select viral or host targets to achieve an antiviral activity as broadly as possible.
Keywords: Chalcogens, sulfur and oxygen-containing compounds, organosulfur compounds, heterocycles, antiviral agents, flavivirus inhibitors.
[http://dx.doi.org/10.1038/s41598-018-30614-3] [PMID: 30104708]
[http://dx.doi.org/10.1016/j.ejmech.2019.07.043] [PMID: 31330449]
[http://dx.doi.org/10.1002/cmdc.201800119] [PMID: 29603634]
[http://dx.doi.org/10.2174/1568026615666150915111741] [PMID: 26369815]
[http://dx.doi.org/10.1007/s41061-018-0184-5] [PMID: 29356979]
[http://dx.doi.org/10.3390/molecules24213839] [PMID: 31731387]
[http://dx.doi.org/10.1128/AAC.47.10.3123-3129.2003] [PMID: 14506019]
[http://dx.doi.org/10.1021/acschembio.9b00675] [PMID: 31868341]
[http://dx.doi.org/10.1016/j.bmcl.2019.03.037] [PMID: 31133531]
[PMID: 25206310]
[http://dx.doi.org/10.3390/molecules26144230] [PMID: 34299505]
[http://dx.doi.org/10.1038/s41586-020-2223-y] [PMID: 32272481]
[http://dx.doi.org/10.1128/AAC.02574-15] [PMID: 26810656]
[http://dx.doi.org/10.1016/S1473-3099(16)30518-7] [PMID: 28011234]
[http://dx.doi.org/10.1016/j.jcv.2016.10.024] [PMID: 27835759]
[http://dx.doi.org/10.1016/j.jcv.2014.08.030] [PMID: 25453327]
[http://dx.doi.org/10.1007/s13365-014-0285-z] [PMID: 25287260]
[http://dx.doi.org/10.1007/s12026-008-8065-6] [PMID: 18841330]
[http://dx.doi.org/10.1038/nrd.2017.33] [PMID: 28473729]
[http://dx.doi.org/10.1021/acs.jmedchem.9b00775] [PMID: 31549836]
[http://dx.doi.org/10.1016/j.antiviral.2018.12.016] [PMID: 30597183]
[http://dx.doi.org/10.1002/cmdc.202000464] [PMID: 32961008]
[http://dx.doi.org/10.4161/hv.26549] [PMID: 24056028]
[http://dx.doi.org/10.3201/eid1901.120458] [PMID: 23259984]
[http://dx.doi.org/10.1016/j.vaccine.2016.02.004] [PMID: 26873054]
[http://dx.doi.org/10.1097/QCO.0000000000000394] [PMID: 28719400]
[http://dx.doi.org/10.3390/life11070615] [PMID: 34202239]
[http://dx.doi.org/10.1371/journal.pbio.3000130] [PMID: 30668574]
[http://dx.doi.org/10.1186/s12879-018-2976-1] [PMID: 29382300]
[http://dx.doi.org/10.4269/ajtmh.18-0426] [PMID: 30226141]
[http://dx.doi.org/10.1021/acs.chemrev.7b00719] [PMID: 29652486]
[http://dx.doi.org/10.1016/j.tips.2013.11.006] [PMID: 24439476]
[http://dx.doi.org/10.1002/med.21664] [PMID: 32060956]
[http://dx.doi.org/10.1016/j.drudis.2021.05.008] [PMID: 34023496]
[http://dx.doi.org/10.1016/j.antiviral.2010.04.014] [PMID: 20452379]
[http://dx.doi.org/10.1146/annurev-med-052915-015720] [PMID: 27686017]
[http://dx.doi.org/10.1016/S0140-6736(18)31311-4] [PMID: 30049419]
[http://dx.doi.org/10.3390/v9110338] [PMID: 29137162]
[http://dx.doi.org/10.1517/17460441.2016.1160887] [PMID: 26966889]
[http://dx.doi.org/10.1073/pnas.0832193100] [PMID: 12759475]
[http://dx.doi.org/10.1016/j.antiviral.2009.09.007] [PMID: 19781577]
[http://dx.doi.org/10.1261/rna.2120410] [PMID: 20980673]
[http://dx.doi.org/10.1146/annurev-virology-110615-042334] [PMID: 27501261]
[http://dx.doi.org/10.1128/AAC.01429-12] [PMID: 23070172]
[http://dx.doi.org/10.1016/j.antiviral.2015.03.014] [PMID: 25842996]
[http://dx.doi.org/10.1021/acs.jmedchem.5b01441] [PMID: 26562070]
[http://dx.doi.org/10.1038/cr.2017.88] [PMID: 28685770]
[PMID: 34472205]
[http://dx.doi.org/10.1128/AAC.02251-12] [PMID: 23403421]
[http://dx.doi.org/10.1002/rmv.1835] [PMID: 25828437]
[http://dx.doi.org/10.1128/AAC.02349-20] [PMID: 34001508]
[http://dx.doi.org/10.1093/nar/gkg277] [PMID: 12654997]
[http://dx.doi.org/10.1016/j.antiviral.2016.09.007] [PMID: 27649989]
[http://dx.doi.org/10.3389/fmicb.2017.00651] [PMID: 28443089]
[http://dx.doi.org/10.1021/acs.jmedchem.9b01779] [PMID: 31972088]
[http://dx.doi.org/10.1002/eji.201040447] [PMID: 20309906]
[http://dx.doi.org/10.1021/acs.jmedchem.8b01403] [PMID: 30721061]
[http://dx.doi.org/10.1021/jm100054f] [PMID: 20334364]
[http://dx.doi.org/10.1074/mcp.R116.065649] [PMID: 28077444]
[http://dx.doi.org/10.1080/22221751.2018.1557988] [PMID: 30866755]
[http://dx.doi.org/10.1016/j.cell.2015.10.046] [PMID: 26582131]
[http://dx.doi.org/10.1016/j.celrep.2017.11.054] [PMID: 29241533]
[http://dx.doi.org/10.1073/pnas.1101143108] [PMID: 21436031]
[http://dx.doi.org/10.1016/j.antiviral.2017.10.001] [PMID: 28982551]
[http://dx.doi.org/10.1128/JVI.02202-15] [PMID: 26676770]
[http://dx.doi.org/10.1128/mBio.00452-17] [PMID: 28465426]
[http://dx.doi.org/10.1371/journal.ppat.1005324] [PMID: 26646986]
[http://dx.doi.org/10.1016/j.chembiol.2018.05.011] [PMID: 29937406]
[http://dx.doi.org/10.1007/978-1-62703-484-5_18] [PMID: 23821272]
[http://dx.doi.org/10.1093/jac/dkp117] [PMID: 19346519]
[http://dx.doi.org/10.1002/cmdc.201000475] [PMID: 21275058]
[http://dx.doi.org/10.1021/jm200153p] [PMID: 21553812]
[http://dx.doi.org/10.1016/j.antiviral.2019.03.004] [PMID: 30849420]
[http://dx.doi.org/10.1021/acsmedchemlett.9b00619] [PMID: 32435384]
[http://dx.doi.org/10.1016/j.ejmech.2020.112992] [PMID: 33208235]
[http://dx.doi.org/10.1371/journal.pntd.0008156] [PMID: 32226028]
[PMID: 34453452]
[http://dx.doi.org/10.1074/jbc.M114.607341] [PMID: 25488659]
[http://dx.doi.org/10.1074/jbc.M110.214189] [PMID: 21349834]
[http://dx.doi.org/10.1074/jbc.M607273200] [PMID: 17287213]
[http://dx.doi.org/10.3390/v3091739] [PMID: 21994804]
[http://dx.doi.org/10.1021/ml400204n]
[http://dx.doi.org/10.1073/pnas.2003056117] [PMID: 32669438]
[http://dx.doi.org/10.1016/j.ejmech.2016.05.043] [PMID: 27240271]
[http://dx.doi.org/10.1021/acsinfecdis.9b00010] [PMID: 31060350]
[http://dx.doi.org/10.1128/JVI.00365-14] [PMID: 24599995]
[http://dx.doi.org/10.1021/jm960072u] [PMID: 8642551]
[http://dx.doi.org/10.1016/j.ejmech.2018.11.017] [PMID: 30496988]
[http://dx.doi.org/10.1016/j.antiviral.2019.02.008] [PMID: 30771406]
[http://dx.doi.org/10.1021/jo502604p] [PMID: 25558884]
[http://dx.doi.org/10.1021/acsmedchemlett.9b00681] [PMID: 32435411]
[http://dx.doi.org/10.1021/acsmedchemlett.8b00583] [PMID: 30996796]
[http://dx.doi.org/10.1039/b904521j] [PMID: 19436915]
[http://dx.doi.org/10.1038/s41586-021-03990-6]
[http://dx.doi.org/10.1126/scitranslmed.abb2181] [PMID: 33536278]