抗艾滋病药物的进展与展望
Journal: Basic Medical Theory Research DOI: 10.12238/bmtr.v6i4.8502
Abstract
目的：HIV是一种T4淋巴细胞和亲神经病毒,它攻击和破坏T4淋巴细胞(T淋巴细胞在细胞免疫系统中起核心作用,促进B细胞产生抗体),导致T4细胞失去正常的免疫功能。然而,目前还没有针对HIV病毒的药物或疫苗,所以可以肯定地说,在21世纪,人类要征服HIV病毒还有很长的路要走。为了让更多的人了解HIV并引起更广泛的关注。方法：查找文献总结并创新。结果：(1)介绍HIV和AIDS流行现状；(2)HIV的复制过程及其目前抗艾滋病毒药物的使用；(3)HIV-1耐药病毒抗病毒药物策略设计；(4)提出抗病毒干预的新靶点和新策略。结论：加强HIV耐药性监测,为有针对性的耐药预防战略提供科学数据,确保抗逆转录病毒治疗的有效性,并减少HIV传播以及发病率和死亡率。
Keywords
HIV；抗病毒治疗；抗病毒药物设计；药物设计目标
Full Text
PDF - Viewed/Downloaded: 0 TimesReferences
[1] .Wu,X.;Wang,J.;Li,Y.;Tang,Y.;Zhao,D.Thoughts on Interven tion in HIV/AIDS with Traditional Chinese Medicine. Journal of Traditional Chinese Medicine 2011,31,265-268, doi:10.1016 /S0254-6272(12)60001-6.
[2] .Voshavar C. Protease Inhibitors for the Treatment of HIV/AIDS: Recent Advances and Future Challenges. Curr Top Med Chem. 2019;19(18):1571-1598. doi:10.2174/1568026619666190619115243
[3] Christensen, D.E.; Ganser-Pornillos, B.K.; Johnson, J.S.; Pornillos, O.; Sundquist, W.I. Reconstitution and Visualizationof HIV-1 Capsid-Dependent Replication and Integration in Vitro.Science 2020,370,eabc8420,doi:10.1126/science.abc8420.
[4] .Kozal, M.; Aberg, J.; Pialoux, G.; Cahn, P.; Thompson, M.; Molina, J.-M.; Grinsztejn, B.; Diaz, R.; Castagna, A.; Kumar, P.; et al. Fostemsavir in Adults with Multidrug-Resistant HIV-1 Infection.N Engl J Med 2020,382,1232-1243,doi:10.1056/NEJM oa1902493.
[5] .PIOT P, ABDOOL KARIM S S, HECHT R.; et al. Defeating AIDS--advancing global health[J/OL].Lancet (London, England), 2015,386(9989):171-218.DOI:10.1016/S0140-6736(15)60658-4.
[6] .El-Brollosy N.R., Jorgensen P.T., Dahan B., Boel A.M., Pedersen E.B.,Nielsen C.Synthesis of novel N-1 (allyloxymeth yl) analogues of 6-benzyl-1-(ethoxymethyl)-5-isopropylura cil (MKC-442, emivirine) with improved activity against HIV-1 and its mutants.J Med Chem.2002;45:5721-5726.
[7] .Pelemans H,Esnouf R,De Clercq E,Balzarini J. Mutatio nal analysis of trp-229 of human immunodeficiency virus type 1 reverse transcriptase (RT) identifies this amino acid residue as a prime target for the rational design of new non-nucleoside RT inhibitors. Mol Pharmacol. 2000 May;57(5): 954-60.PMID:10779379.
[8] .Alcamí,J.Ciclo replicativo del VIH. Dianas terapéutic as consolidadas y dianas potenciales. Enfermedades Infeccio sas y Microbiología Clínica 2008,26,3–10,doi:10.1016/S0213-005X(08)76566-2.
[9] PIOT P, ABDOOL KARIM S S, HECHT R.; et al. Defeating AIDS--advancing global health[J/OL].Lancet (London, England), 2015,386(9989):171-218.DOI:10.1016/S0140-6736(15)60658-4.
[10] .GROBLER J A, STILLMOCK K, HU B.; et al. Diketo acid inhibitor mechanism and HIV-1 integrase: implications for metal binding in the active site of phosphotransferase enzy mes[J/OL]. Proceedings of the National Academy of Sciences of the United States of America, 2002, 99(10): 6661-6666. DOI:10.1073/pnas.092056199.
[11] .Hare S.,Gupta S.S., Valkov E., Engelman A., Cherepanov P. Retroviral intasome assembly and inhibition of DNA strand transfer.Nature.2010;464:232-236.
[12] .Kobayashi M.; Yoshinaga T.; Seki T.; Wakasa-Morimoto C.;Brown K.W.;Ferris R.;Foster S.A.;Hazen R.J.;Miki S.;SuyamaKagitani A.; Kawauchi-Miki S.; Taishi T.; Kawasuji T.; Johns B.A.; Underwood M. R.; Garvey E. P.; Sato A.; Fujiwara T.In vitroantiretroviral properties of S/GSK1349572, a next-generati on HIV integrase inhibitor.Antimicrob.Agents Chemother.2011, 55,813-821.
[13] .Kumar,Mukesh etal.“Visualizing Tetrahedral Oxyani on Bound in HIV-1 Protease Using Neutrons: Implications for the Catalytic Mechanism and Drug Design.”ACS omega vol. 5,2011605-11617.14 May.2020,doi:10.1021/acsomega.0c00835.
[14] Matarrese P,Tinari A,Gambardella L,Mormone E, Narilli P,Pierdominici M,Cauda R,Malorni W.Antivir Ther.2005;10(Suppl2):M29.
[15] .PIOT P, ABDOOL KARIM S S, HECHT R.; et al. Defeating AIDS--advancing global health[J/OL].Lancet (London, England), 2015,386(9989):171-218.DOI:10.1016/S0140-6736(15)60658-4.
[16] .Harrison S.C. Viral membrane fusion. Nat. Struct. Mol. Biol.2008;15:690-698.doi:10.1038/nsmb.1456.
[17] Berger EA, Doms RW, Fenyö EM, Korber BT, Littman DR, Moore JP,etal.A new classification for HIV-1.Nature(1998)391: 240.10.1038/34571.
[18] .Van Der Ryst E. Maraviroc - A CCR5 Antagonist for the Treatment of HIV-1 Infection. Front Immunol. 2015 Jun 5;6:277. doi: 10.3389/fimmu.2015.00277. PMID: 26097475; PMCID:PMC4456946.
[19] .Doms R.W. Beyond receptor expression: The influence of receptor conformation, density, and affinity in HIV-1 infection.Virology.2000;276:229–237.doi:10.1006/viro.2000.0612.
[20] .KILBY J M, HOPKINS S, VENETTA T M.; et al. Potent suppression of HIV-1 replication in humans by T-20, a pept ide inhibitor of gp41-mediated virus entry[J/OL]. Nature Medicine,1998,4(11):1302-1307.DOI:10.1038/3293.
[21] .Yates,M.K.;Seley-Radtke,K.L.The Evolution of Antivi ral Nucleoside Analogues:A Review for Chemists and Non-Chem ists. Part II:Complex Modifications to the Nucleoside Scaffold.Antiviral Research 2019,162,5–21,doi:10.1016/j.antiviral.2018. 11.016.
[22] .Darbyshire,J.; Foulkes, M.; Peto, R.; Duncan, W.; Babiker,A.; Collins, R.; Hughes, M.; Peto, T.E.; Walker, S.A. Zidovudine (AZT)versus AZT plus Didanosine(DdI)versus AZT plus Zalcitab ine (DdC) in HIV Infected Adults. Cochrane Database of Systematic Reviews 2000,2010,doi:10.1002/14651858.CD002038.
[23] .Stantchev, T.S.; Markovic, I.; Telford, W.G.; Clouse, K.A.; Broder, C.C. The Tyrosine Kinase Inhibitor Genistein Blocks HIV-1 Infection in Primary Human Macrophages. Virus Research 2007,123,178-189,doi:10.1016/j.virusres.2006.09.004.
[24] .Guendel, I.; Agbottah, E.T.; Kehn-Hall, K.; Kashanchi, F. Inhibition of Human Immunodeficiency Virus Type-1 by Cdk Inhibitors.AIDS Res Ther 2010,7,7,doi:10.1186/1742-6405-7-7.
[2] .Voshavar C. Protease Inhibitors for the Treatment of HIV/AIDS: Recent Advances and Future Challenges. Curr Top Med Chem. 2019;19(18):1571-1598. doi:10.2174/1568026619666190619115243
[3] Christensen, D.E.; Ganser-Pornillos, B.K.; Johnson, J.S.; Pornillos, O.; Sundquist, W.I. Reconstitution and Visualizationof HIV-1 Capsid-Dependent Replication and Integration in Vitro.Science 2020,370,eabc8420,doi:10.1126/science.abc8420.
[4] .Kozal, M.; Aberg, J.; Pialoux, G.; Cahn, P.; Thompson, M.; Molina, J.-M.; Grinsztejn, B.; Diaz, R.; Castagna, A.; Kumar, P.; et al. Fostemsavir in Adults with Multidrug-Resistant HIV-1 Infection.N Engl J Med 2020,382,1232-1243,doi:10.1056/NEJM oa1902493.
[5] .PIOT P, ABDOOL KARIM S S, HECHT R.; et al. Defeating AIDS--advancing global health[J/OL].Lancet (London, England), 2015,386(9989):171-218.DOI:10.1016/S0140-6736(15)60658-4.
[6] .El-Brollosy N.R., Jorgensen P.T., Dahan B., Boel A.M., Pedersen E.B.,Nielsen C.Synthesis of novel N-1 (allyloxymeth yl) analogues of 6-benzyl-1-(ethoxymethyl)-5-isopropylura cil (MKC-442, emivirine) with improved activity against HIV-1 and its mutants.J Med Chem.2002;45:5721-5726.
[7] .Pelemans H,Esnouf R,De Clercq E,Balzarini J. Mutatio nal analysis of trp-229 of human immunodeficiency virus type 1 reverse transcriptase (RT) identifies this amino acid residue as a prime target for the rational design of new non-nucleoside RT inhibitors. Mol Pharmacol. 2000 May;57(5): 954-60.PMID:10779379.
[8] .Alcamí,J.Ciclo replicativo del VIH. Dianas terapéutic as consolidadas y dianas potenciales. Enfermedades Infeccio sas y Microbiología Clínica 2008,26,3–10,doi:10.1016/S0213-005X(08)76566-2.
[9] PIOT P, ABDOOL KARIM S S, HECHT R.; et al. Defeating AIDS--advancing global health[J/OL].Lancet (London, England), 2015,386(9989):171-218.DOI:10.1016/S0140-6736(15)60658-4.
[10] .GROBLER J A, STILLMOCK K, HU B.; et al. Diketo acid inhibitor mechanism and HIV-1 integrase: implications for metal binding in the active site of phosphotransferase enzy mes[J/OL]. Proceedings of the National Academy of Sciences of the United States of America, 2002, 99(10): 6661-6666. DOI:10.1073/pnas.092056199.
[11] .Hare S.,Gupta S.S., Valkov E., Engelman A., Cherepanov P. Retroviral intasome assembly and inhibition of DNA strand transfer.Nature.2010;464:232-236.
[12] .Kobayashi M.; Yoshinaga T.; Seki T.; Wakasa-Morimoto C.;Brown K.W.;Ferris R.;Foster S.A.;Hazen R.J.;Miki S.;SuyamaKagitani A.; Kawauchi-Miki S.; Taishi T.; Kawasuji T.; Johns B.A.; Underwood M. R.; Garvey E. P.; Sato A.; Fujiwara T.In vitroantiretroviral properties of S/GSK1349572, a next-generati on HIV integrase inhibitor.Antimicrob.Agents Chemother.2011, 55,813-821.
[13] .Kumar,Mukesh etal.“Visualizing Tetrahedral Oxyani on Bound in HIV-1 Protease Using Neutrons: Implications for the Catalytic Mechanism and Drug Design.”ACS omega vol. 5,2011605-11617.14 May.2020,doi:10.1021/acsomega.0c00835.
[14] Matarrese P,Tinari A,Gambardella L,Mormone E, Narilli P,Pierdominici M,Cauda R,Malorni W.Antivir Ther.2005;10(Suppl2):M29.
[15] .PIOT P, ABDOOL KARIM S S, HECHT R.; et al. Defeating AIDS--advancing global health[J/OL].Lancet (London, England), 2015,386(9989):171-218.DOI:10.1016/S0140-6736(15)60658-4.
[16] .Harrison S.C. Viral membrane fusion. Nat. Struct. Mol. Biol.2008;15:690-698.doi:10.1038/nsmb.1456.
[17] Berger EA, Doms RW, Fenyö EM, Korber BT, Littman DR, Moore JP,etal.A new classification for HIV-1.Nature(1998)391: 240.10.1038/34571.
[18] .Van Der Ryst E. Maraviroc - A CCR5 Antagonist for the Treatment of HIV-1 Infection. Front Immunol. 2015 Jun 5;6:277. doi: 10.3389/fimmu.2015.00277. PMID: 26097475; PMCID:PMC4456946.
[19] .Doms R.W. Beyond receptor expression: The influence of receptor conformation, density, and affinity in HIV-1 infection.Virology.2000;276:229–237.doi:10.1006/viro.2000.0612.
[20] .KILBY J M, HOPKINS S, VENETTA T M.; et al. Potent suppression of HIV-1 replication in humans by T-20, a pept ide inhibitor of gp41-mediated virus entry[J/OL]. Nature Medicine,1998,4(11):1302-1307.DOI:10.1038/3293.
[21] .Yates,M.K.;Seley-Radtke,K.L.The Evolution of Antivi ral Nucleoside Analogues:A Review for Chemists and Non-Chem ists. Part II:Complex Modifications to the Nucleoside Scaffold.Antiviral Research 2019,162,5–21,doi:10.1016/j.antiviral.2018. 11.016.
[22] .Darbyshire,J.; Foulkes, M.; Peto, R.; Duncan, W.; Babiker,A.; Collins, R.; Hughes, M.; Peto, T.E.; Walker, S.A. Zidovudine (AZT)versus AZT plus Didanosine(DdI)versus AZT plus Zalcitab ine (DdC) in HIV Infected Adults. Cochrane Database of Systematic Reviews 2000,2010,doi:10.1002/14651858.CD002038.
[23] .Stantchev, T.S.; Markovic, I.; Telford, W.G.; Clouse, K.A.; Broder, C.C. The Tyrosine Kinase Inhibitor Genistein Blocks HIV-1 Infection in Primary Human Macrophages. Virus Research 2007,123,178-189,doi:10.1016/j.virusres.2006.09.004.
[24] .Guendel, I.; Agbottah, E.T.; Kehn-Hall, K.; Kashanchi, F. Inhibition of Human Immunodeficiency Virus Type-1 by Cdk Inhibitors.AIDS Res Ther 2010,7,7,doi:10.1186/1742-6405-7-7.
Copyright © 2024 阮孟泽
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License