An overall picture of SARS coronavirus (SARS-CoV) genome-encoded major proteins: Structures, functions and drug development

Current Pharmaceutical Design

Volumn 12, Issue 35, 2006, Pages 4539-4553

  Chen, Shuai ^a   Luo, Haibin ^a   Chen, Lili ^a   Chen, Jing ^a   Shen, Jianhua ^a   Zhu, Weiliang ^a   Chen, Kaixian ^a   Shen, Xu ^a,b   Jiang, Hualiang ^a,b  

^a SHANGHAI INSTITUTE OF MATERIA MEDICA   (China)

^b EAST CHINA UNIVERSITY OF SCIENCE AND TECHNOLOGY   (China)

Author keywords

Atypical pneumonia; Inhibitor design and screening; SARS coronavirus; SARS CoV genome encoded major proteins; Structural and functional characterization; Structure based drug development

Indexed keywords

ADENOSINE TRIPHOSPHATASE; ALPHA GLUCOSIDASE INHIBITOR; ANTIVIRUS AGENT; BORONIC ACID DERIVATIVE; CALANOLIDE A; CINANSERIN; CYSTEINE PROTEINASE; DNA VACCINE; GLYCOVIR; HELICASE; HEXACHLOROPHENE; KZ 7088; L 417; L 700; MONOCLONAL ANTIBODY; NATURAL PRODUCT; NEVIRAPINE; NUCLEOCAPSID PROTEIN; PHENYLMERCURIC ACETATE; PROTEINASE INHIBITOR; RIBAVIRIN; RNA DIRECTED RNA POLYMERASE; SABADININE; SEVERE ACUTE RESPIRATORY SYNDROME VACCINE; SMALL INTERFERING RNA; THIOMERSAL; UNINDEXED DRUG; VIRUS PROTEIN; VIRUS RNA; VIRUS SPIKE PROTEIN;

CHINA; COOPERATION; DISEASE SEVERITY; DRUG DESIGN; DRUG RESEARCH; DRUG TARGETING; ENZYME ACTIVITY; ENZYME SPECIFICITY; HUMAN; INFECTION CONTROL; MASS SPECTROMETRY; MEDICAL RESEARCH; NONHUMAN; OPEN READING FRAME; PATHOGENESIS; PHYLOGENY; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN FUNCTION; PROTEIN STRUCTURE; PUBLIC HEALTH SERVICE; REVIEW; SARS CORONAVIRUS; SEVERE ACUTE RESPIRATORY SYNDROME; VERO CELL; VIROGENESIS; VIRUS PNEUMONIA; WORLD HEALTH ORGANIZATION;

ANTIVIRAL AGENTS; CYSTEINE ENDOPEPTIDASES; DRUG DESIGN; GENOME, VIRAL; MEMBRANE GLYCOPROTEINS; MODELS, MOLECULAR; NUCLEOCAPSID PROTEINS; PROTEIN CONFORMATION; SARS VIRUS; VIRAL ENVELOPE PROTEINS; VIRAL MATRIX PROTEINS; VIRAL NONSTRUCTURAL PROTEINS; VIRAL PROTEINS; VIRAL VACCINES;

EID: 33751509079     PISSN: 13816128     EISSN: None     Source Type: Journal    
DOI: 10.2174/138161206779010459     Document Type: Review

References (106)

1. Rota PA, Oberste MS, Monroe SS, Nix WA, Campagnoli R, Icenogle JP, et al. Characterization of a novel coronavirus associated with severe acute respiratory syndrome. Science 2003; 300: 1394-1399.
2. Siddel SG. The Coronaviridae. New York: Plenum Press 1995.
3. Ziebuhr J. Molecular biology of severe acute respiratory syndrome coronavirus. Curr Opin Microbiol 2004; 7: 412-419.
4. Marra MA, Jones SJ, Astell CR, Holt RA, Brooks-Wilson A, Butterfield YS, et al. The Genome sequence of the SARS-associated coronavirus. Science 2003; 300: 1399-1404.
5. Thiel V, Ivanov KA, Putics A, Hertzig T, Schelle B, Bayer S, et al. Mechanisms and enzymes involved in SARS coronavirus genome expression. J Gen Virol 2003; 84: 2305-2315.
6. Ziebuhr J, Heusipp G, Siddell SG. Biosynthesis, purification, and characterization of the human coronavirus 229E 3C-like proteinase. J Virol 1997; 71: 3992-3997.
7. Dougherty WG, Semler BL. Expression of virus-encoded proteinases: functional and structural similarities with cellular enzymes. Microbiol Rev 1993; 57: 781-822.
8. Ziebuhr J, Snijder EJ, Gorbalenya AE. Virus-encoded proteinases and proteolytic processing in the Nidovirales. J Gen Virol 2000; 81: 853-879.
9. pro) structure: basis for design of anti-SARS drugs. Science 2003; 300: 1763-1767.
10. Sun HF, Luo HB, Yu CY, Sun T, Chen J, Peng SY, et al. Molecular cloning, expression, purification, and mass spectrometric characterization of 3C-like protease of SARS coronavirus. Protein Exp Purif 2003; 32: 302-308.
11. Xiong B, Gui CS, Xu XY, Luo C, Chen J, Luo HB, et al. A 3D model of SARS-CoV 3CL proteinase and its inhibitors design by virtual screening. Acta Pharmacol Sin 2003; 24: 497-504.
12. Yang HT, Yang MJ, Ding Y, Liu YW, Lou ZY, Zhou Z, et al. The crystal structures of severe acute respiratory syndrome virus main protease and its complex with an inhibitor. Proc Natl Acad Sci USA 2003; 100: 13190-13195.
13. Anand K, Plam GJ, Mesters JR, Siddell SG, Ziebuhr J, Higenfeld R. Structure of coronavirus main proteinase reveals combination of a chymotrypsin fold with an extra alpha-helical domain. EMBO J 2002; 21: 3213-3224.
14. Shi JH, Wei Z, Song JX. Dissection study on the SARS 3C-like protease reveals the critical role of the extra domain in dimerization of the enzyme: Defining the extra domain as a new target for design of highly-specific protease inhibitors. J Biol Chem 2004; 279: 24765-24773.
15. pro N-terminus is Indispensable for Proteolytic Activity but Not for Enzyme Dimerization: Biochemical and Thermodynamic Investigation in Conjunction with Molecular Dynamics Simulations. J Biol Chem 2005; 280: 164-173.
16. Fan KQ, Wei P, Feng Q, Chen SD, Huang CK, Ma L, et al. Biosynthesis, purification, and substrate specificity of severe acute respiratory syndrome coronavirus 3C-like proteinase. J Biol Chem 2004; 279: 1637-1642.
17. Chou CY, Chang HC, Hsu WC, Lin TZ, Lin CH, Chang GG. Quaternary structure of the severe acute respiratory syndrome (SARS) coronavirus main protease. Biochemistry 2004; 43: 14958-14970.
18. Gao F, Ou HY, Chen LL, Zheng WX, Zhang CT. Prediction of proteinase cleavage sites in polyproteins of coronaviruses and its applications in analyzing SARS-CoV genomes. FEBS Lett 2003; 553: 451-456.
19. Hegyi A, Ziebuhr J. Conservation of substrate specificities among coronavirus main proteases. J Gen Virol 2002; 83: 595-599.
20. Huang CK, Wei P, Fan KQ, Liu Y, Lai LH. 3C-like proteinase from SARS coronavirus catalyzes substrate hydrolysis by a general base mechanism. Biochemistry 2004; 43: 4568-4573.
21. Kuo CJ, Chi YH, Hsu JA, Liang PH. Characterization of SARS main protease and inhibitor assay using a fluorogenic substrate. Biochem Biophys Res Commun 2004; 318: 862-867.
22. pro) by fluorescence resonance energy transfer (FRET) technique. Acta Pharmacol Sin 2005; 26: 99-107.
23. pro protease: basis for the in vitro screening of anti-SARS drugs. FEBS Lett 2004; 574: 131-137.
24. Jenwitheesuk E, Samudrala R. Identifying inhibitors of the SARS coronavirus proteinase. Bioorg Med Chem Lett 2004; 13: 3989-3992.
25. Toney JH, Navas-Martin S, Weiss SR, Koeller A. Sabadinine: A Potential Non-Peptide Anti-Severe Acute-Respiratory-Syndrome Agent Identified Using Structure-Aided Design. J Med Chem 2004; 47: 1079-1080.
26. Zhang XW, Yap YL. Exploring the binding mechanism of the main proteinase in SARS-associated coronavirus and its implication to anti-SARS drug design. Bioorg Med Chem 2004; 12: 2219-2223.
27. Kao RY, To PC, Ng WY, Tsui HW, Lee SW, Tsoi HW, et al. Characterization of SARS-CoV main protease and identification of biologically active small molecule inhibitors using a continuous fluorescence-based assay. FEBS Lett 2004; 576: 325-330.
28. pro. Biochemistry 2004; 43: 4906-4912.
29. Blanchard JE, Elowe NH, Huitema C, Fortin PD, Cechetto JD, Eltis LD, et al. High-Throughput screening identifies inhibitors of the SARS coronavirus main proteinase. Chem Biol 2004; 11: 1445-1453.
30. Wu CY, Jan JT, Ma SH, Kuo CJ, Juan HF, Cheng YS, et al. Small molecules targeting severe acute respiratory syndrome human coronavirus. Proc Natl Acad Sci USA 2004; 101: 10012-10017.
31. Lee VS, Wittayanarakul K, Remsungnen T, Parasuk V, Sompornpisut P, Chantratita W, et al. Structure and dynamics of SARS coronavirus proteinase: the primary key to the designing and screening for anti-SARS drugs. Sci Asia 2003; 29: 181-188.
32. Sirois S, Wei DQ, Du QS, Chou KC. Virtual screening for SARS-CoV protease based on KZ7088 pharmacophore points. J Chem Inf Comput Sci 2004; 44: 1111-1122.
33. Hsu TA, Kuo CJ, Hsieh HP, Wang YC, Huang KK, Lin PC, et al. Evaluation of metal-conjugated compounds as inhibitors of 3CL protease of SARS-CoV. FEBS Lett 2004; 574: 116-120.
34. Chen LL, Gui CS, Luo XM, Yang QG, Gunther S, Scandella E, et al. The old drug cinanserin is an inhibitor of the 3C-like proteinase of SARS coronavirus and strongly reduces virus replication in vitro. J Virol 2005; 79: 7095-7103.
35. Han DP, Kim HG, Kim YB, Poon LL, Cho MW. Development of a safe neutralization assay for SARS-CoV and characterization of S-glycoprotein. Virology 2004; 326: 140-149.
36. Li W, Moore MJ, Vasilieva N, Sui J, Wong SK, Berne MA, et al. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature 2003; 426: 450-454.
37. Wang P, Chen J, Zheng A, Nie Y, Shi X, Wang W, et al. Expression cloning of functional receptor used by SARS coronavirus. Biochem Biophys Res Commun 2004; 315: 439-444.
38. Wong SK, Li W, Moore MJ, Choe H, Farzan M. A 193-amino acid fragment of the SARS coronavirus S protein efficiently binds angiotensin-converting enzyme 2. J Biol Chem 2004; 279: 3197-3201.
39. Xiao X, Chakraborti S, Dimitrov AS, Gramatikoff K, Dimitrov DS. The SARS-CoV S glycoprotein: expression and functional characterization. Biochem Biophys Res Commun 2003; 312: 1159-1164.
40. Babcock GJ, Esshaki DJ, Thomas WD, Ambrosino DM. Amino acids 270 to 510 of the severe acute respiratory syndrome coronavirus spike protein are required for interaction with receptor. J Virol 2004; 78: 4552-4560.
41. Ho TY, Wu SL, Cheng SE, Wei YC, Huang SP, Hsiang CY. Antigenicity and receptor-binding ability of recombinant SARS coronavirus spike protein. Biochem Biophys Res Commun 2004; 313: 938-947.
42. Sui J, Li W, Murakami A, Tamin A, Matthews LJ, Wong SK, et al. Potent neutralization of severe acute respiratory syndrome (SARS) coronavirus by a human mAb to S1 protein that blocks receptor association. Proc Natl Acad Sci USA 2004; 101: 2536-2541.
43. Zhang Y, Li T, Fu L, Yu C, Li Y, Xu X, et al. Silencing SARS-CoV Spike protein expression in cultured cells by RNA interference. FEBS Lett 2004; 560: 141-146.
44. Yang ZY, Kong WP, Huang Y, Roberts A, Murphy BR, Subbarao K, et al. A DNA vaccine induces SARS coronavirus neutralization and protective immunity in mice. Nature 2004; 428: 561-564.
45. Dimitrov DS. The secret life of ACE2 as a receptor for the SARS virus. Cell 2003; 115: 652-653.
46. Yu C, Gui C, Luo H, Chen L, Zhang L, Yu H, et al. Folding of the SARS Coronavirus Spike Glycoprotein Immunological Fragment (SARS_S1b): Thermodynamic and Kinetic Investigation Correlating with Three-Dimensional Structural Modeling. Biochemistry 2005; 44: 1453-1463.
47. Spiga O, Bernini A, Ciutti A, Chiellini S, Menciassi N, Finetti F, et al. Molecular modelling of S1 and S2 subunits of SARS coronavirus spike glycoprotein. Biochem Biophys Res Commun 2003; 310: 78-83.
48. Kubo H, Takase-Yoden S, Taguchi F. Neutralization and fusion inhibition activities of monoclonal antibodies specific for the S1 subunit of the spike protein of neurovirulent murine coronavirus JHMV c1-2 variant. J Gen Virol 1993; 74(7): 1421-1425.
49. Xu Y, Lou Z, Liu Y, Pang H, Tien P, Gao GF, et al. Crystal Structure of Severe Acute Respiratory Syndrome Coronavirus Spike Protein Fusion Core. J Biol Chem 2004; 279: 49414-49419.
50. Liu S, Xiao G, Chen Y, He Y, Niu J, Escalante CR, et al. Interaction between heptad repeat 1 and 2 regions in spike protein of SARS-associated coronavirus: implications for virus fusogenic mechanism and identification of fusion inhibitors. Lancet 2004; 363: 938-947.
51. Ingallinella P, Bianchi E, Finotto M, Cantoni G, Eckert DM, Supekar VM, et al. Structural characterization of the fusion-active complex of severe acute respiratory syndrome (SARS) coronavirus. Proc Natl Acad Sci USA 2004; 101: 8709-8714.
52. Lu M, Blacklow SC, Kim PS. A trimeric structural domain of the HIV-1 transmembrane glycoprotein. Nat Struct Biol 1995; 2: 1075-1082.
53. Luo H, Ye F, Sun T, Yue L, Peng S, Chen J, et al. In vitro biochemical and thermodynamic characterization of nucleocapsid protein of SARS. Biophys Chem 2004; 112: 15-25.
54. Wang Y, Wu X, Wang Y, Li B, Zhou H, Yuan G, et al. Low stability of nucleocapsid protein in SARS virus. Biochemistry 2004; 43: 11103-11108.
55. He R, Dobie F, Ballantine M, Leeson A, Li Y, Bastien N, et al. Analysis of multimerization of the SARS coronavirus nucleocapsid protein. Biochem Biophys Res Commun 2004; 316: 476-483.
56. Surjit M, Liu B, Kumar P, Chow VT, Lal SK. The nucleocapsid protein of the SARS coronavirus is capable of self-association through a C-terminal 209 amino acid interaction domain. Biochem Biophys Res Commun 2004; 317: 1030-1036.
57. Luo HB, Ye F, Chen KX, Shen X, Jiang HL. SR-rich motif plays a pivotal role in recombinant SARS coronavirus nucleocapsid protein multimerization. Biochemistry 2005; 44: 15351-15358.
58. Luo C, Luo H, Zheng S, Gui C, Yue L, Yu C, et al. Nucleocapsid protein of SARS coronavirus tightly binds to human cyclophilin A. Biochem Biophys Res Commun 2004; 321: 557-565.
59. Luban J, Bossolt KL, Franke EK, Kalpana GV, Goff SP. Human immunodeficiency virus type 1 Gag protein binds to cyclophilins A and B. Cell 1993; 73: 1067-1078.
60. Braaten D, Luban J. Cyclophilin A regulates HIV-1 infectivity, as demonstrated by gene targeting in human T cells. EMBO J 2001; 20: 1300-1309.
61. Luo HB, Chen Q, Chen J, Chen KX, Shen X, Jiang HL. The nucleocapsid protein of SARS coronavirus (SARS_N) has a high binding affinity to the human cellular heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1). FEBS Lett 2005; 579: 2623-2628.
62. Shi ST, Huang P, Li HP, Lai MM. Heterogeneous nuclear ribonucleoprotein A1 regulates RNA synthesis of a cytoplasmic virus. EMBO J 2000; 19: 4701-4711.
63. Nelson GW, Stohlman SA, Tahara SM. High affinity interaction between nucleocapsid protein and leader/intergenic sequence of mouse hepatitis virus RNA. J Gen Virol 2000; 81: 181-188.
64. Huang Q, Yu L, Petros AM, Gunasekera A, Liu Z, Xu N, et al. Structure of the N-terminal RNA-binding domain of the SARS CoV nucleocapsid protein. Biochemistry 2004; 43: 6059-6063.
65. De Haan CA, Kuo L, Masters PS, Vennema H, Rottier PJ. Coronavirus particle assembly: primary structure requirements of the membrane protein. J Virol 1998; 72: 6838-6850.
66. De Haan CA, Vennema H, Rottier PJ. Assembly of the coronavirus envelope: homotypic interactions between the M proteins. J Virol 2000; 74: 4967-4978.
67. Kuo L and Masters PS. Genetic evidence for a structural interaction between the carboxy termini of the membrane and nucleocapsid proteins of mouse hepatitis virus. J Virol 2002; 76: 4987-4999.
68. Escors D, Ortego J, Laude H, Enjuanes L. The membrane M protein carboxy terminus binds to transmissible gastroenteritis coronavirus core and contributes to core stability. J Virol 2001; 75: 1312-1324.
69. He R, Leeson A, Ballantine M, Andonov A, Baker L, Dobie F, et al. Characterization of protein-protein interactions between the nucleocapsid protein and membrane protein of the SARS coronavirus. Virus Res 2004; 105: 121-125.
70. Luo HB, Wu DL, Shen C, Chen KX, Shen X, et al. Severe acute respiratory syndrome coronavirus membrane protein interacts with nucleocapsid protein mostly through their carboxyl termini by electrostatic attraction. Int J Biochem Cell Biol 2006; 38: 589-599.
71. Baudoux P, Carrat C, Besnardeau L, Charley B, Laude H. Coronavirus pseudoparticles formed with recombinant M and E proteins induce alpha interferon synthesis by leukocytes. J Virol 1998; 72: 8636-8643.
72. De Haan CA, De Wit M, Kuo L, Montalto C, Masters PS, Weiss SR, et al. O-glycosylation of the mouse hepatitis coronavirus membrane protein. Virus Res 2002; 82: 77-81.
73. Arbely E, Khattari Z, Brotons G, Akkawi M, Salditt T, Arkin IT. A highly unusual palindromic transmembrane helical hairpin formed by SARS coronavirus E protein. J Mol Biol 2004; 341: 769-779.
74. Raamsman MJ, Locker JK, De Hooge A, De Vries AA, Griffiths G, Vennema H, et al. Characterization of the coronavirus mouse hepatitis virus strain A59 small membrane protein E. J Virol 2000; 74: 2333-2342.
75. Corse E and Machamer CE. Infectious bronchitis virus E protein is targeted to the Golgi complex and directs release of virus-like particles. J Virol 2000; 74: 4319-4326.
76. Maeda J, Repass JF, Maeda A, Makino S. Membrane topology of coronavirus E protein. Virology 2001; 281: 163-169.
77. Shen X, Xue JH, Yu CY, Luo HB, Qin L, Yu XJ, et al. Small envelope protein E of SARS: cloning, expression, purification, CD determination, and bioinformatics analysis. Acta Pharmacol Sin 2003; 24: 505-511.
78. An S, Chen CJ, Yu X, Leibowitz JL, Makino S. Induction of apoptosis in murine coronavirus-infected cultured cells and demonstration of E protein as an apoptosis inducer. J Virol 1999; 73: 7853-7859.
79. Godet M, L'Haridon R, Vautherot JF, Laude H. TGEV corona virus ORF4 encodes a membrane protein that is incorporated into virions. Virology 1992; 188: 666-675.
80. Kuo L, Masters PS. The small envelope protein E is not essential for murine coronavirus replication. J Virol 2003; 77: 4597-4608.
81. Risco C, Muntion M, Enjuanes L, Carrascosa JL. Two types of virus-related particles are found during transmissible gastroenteritis virus morphogenesis. J Virol 1998; 72: 4022-4031.
82. Salanueva IJ, Carrascosa JL, Risco C. Structural maturation of the transmissible gastroenteritis coronavirus. J Virol 1999; 73: 7952-7964.
83. Tooze J, Tooze S, Warren G. Replication of coronavirus MHVA59 in sac- cells: determination of the first site of budding of progeny virions. Eur J Cell Biol 1984; 33: 281-293.
84. Vennema H, Godeke GJ, Rossen JW, Voorhout WF, Horzinek MC, Opstelten DJ, et al. Nucleocapsid-independent assembly of coronavirus-like particles by co-expression of viral envelope protein genes. EMBO J 1996; 15: 2020-2028.
85. Maeda J, Maeda A, Makino S. Release of coronavirus E protein in membrane vesicles from virus-infected cells and E protein-expressing cells. Virology 1999; 263: 265-272.
86. Fischer F, Stegen CF, Masters PS, Samsonoff WA. Analysis of constructed E gene mutants of mouse hepatitis virus confirms a pivotal role for E protein in coronavirus assembly. J Virol 1998; 72: 7885-7894.
87. Ho Y, Lin PH, Liu CY, Lee SP, Chao YC. Assembly of human severe acute respiratory syndrome coronavirus-like particles. Biochem Biophys Res Commun 2004, 318: 833-838.
88. Wilson L, McKinlay C, Gage P, Ewart G. SARS coronavirus E protein forms cation-selective ion channels. Virology 2004; 330: 322-331.
89. Liao Y, Lescar J, Tam JP, Liu DX. Expression of SARS-coronavirus envelope protein in Escherichia coli cells alters membrane permeability. Biochem Biophys Res Commun 2004; 325: 374-380.
90. Snijder EJ, Bredenbeek PJ, Dobbe JC, Thiel V, Ziebuhr J, Poon LL, et al. Unique and conserved features of genome and proteome of SARS-coronavirus, an early split-off from the coronavirus group 2 lineage. J Mol Biol 2003; 331: 991-1004.
91. Tan YJ, Lim SG, Hong W. Characterization of viral proteins encoded by the SARS-coronavirus genome. Antiviral Res 2005; 65: 69-78.
92. Egloff MP, Ferron F, Campanacci V, Longhi S, Rancurel C, Dutartre H, et al. The severe acute respiratory syndromecoronavirus replicative protein nsp9 is a single-stranded RNA-binding subunit unique in the RNA virus world. Proc Natl Acad Sci USA 2004; 101: 3792-3796.
93. Sutton G, Fry E, Carter L, Sainsbury S, Walter T, Nettleship J, et al. The nsp9 replicase protein of SARS-coronavirus, structure and functional insights. Structure (Camb) 2004; 12: 341-353.
94. Carroll SS, Tomassini JE, Bosserman M, Getty K, Stahlhut MW, Eldrup AB, et al. Inhibition of hepatitis C virus RNA replication by 2′-modified nucleoside analogs. J Biol Chem 2003; 278: 11979-11984.
95. Dhanak D, Duffy KJ, Johnston VK, Lin-Goerke J, Darcy M, Shaw AN, et al. Identification and biological characterization of heterocyclic inhibitors of the hepatitis C virus RNA-dependent RNA polymerase. J Biol Chem 2002; 277: 38322-38327.
96. Azzi A and Lin SX. Human SARS-coronavirus RNA-dependent RNA polymerase: activity determinants and nucleoside analogue inhibitors. Proteins 2004; 57: 12-14.
97. Xu X, Liu Y, Weiss S, Arnold E, Sarafianos SG, Ding J. Molecular model of SARS coronavirus polymerase: implications for biochemical functions and drug design. Nucleic Acids Res 2003; 31: 7117-7130.
98. Tanner JA, Watt RM, Chai YB, Lu LY, Lin MC, Peiris JS, et al. The severe acute respiratory syndrome (SARS) coronavirus NTPase/helicase belongs to a distinct class of 5′ to 3′ viral helicases. J Biol Chem 2003; 278: 39578-39582.
99. Ivanov KA, Thiel V, Dobbe JC, Van der MY, Snijder EJ, Ziebuhr J. Multiple enzymatic activities associated with severe acute respiratory syndrome coronavirus helicase. J Virol 2004; 78: 5619-5632.
100. Kleymann G, Fischer R, Betz UA, Hendrix M, Bender W, Schneider U, et al. New helicase-primase inhibitors as drug candidates for the treatment of herpes simplex disease. Nat Med 2002; 8: 392-398.
101. Crute JJ, Grygon CA, Hargrave KD, Simoneau B, Faucher AM, Bolger G, et al. Herpes simplex virus helicase-primase inhibitors are active in animal models of human disease. Nat Med 2002; 8: 386-391.
102. Borowski P, Schalinski S, Schmitz H. Nucleotide triphosphatase/helicase of hepatitis C virus as a target for antiviral therapy. Antiviral Res 2002; 55: 397-412.
103. Von Grotthuss M, Wyrwicz LS, Rychlewski L. mRNA cap-1 methyltransferase in the SARS genome. Cell 2003; 113: 701-702.
104. Callanan M. Mining the probiotic genome: advanced strategies, enhanced benefits, perceived obstacles. Curr Pharm Des 2005; 11(1): 25-36.
105. Gomez J, Nadal A, Sabariegos R, Beguiristain N, Martell M, Piron M. Three properties of the hepatitis C virus RNA genome related to antiviral strategies based on RNA-therapeutics: variability, structural conformation and tRNA mimicry. Curr Pharm Des 2004; 10(30): 3741-56.
106. Martinez-Salas E, Fernandez-Miragall O. Picornavirus IRES: structure function relationship. Curr Pharm Des 2004; 10(30): 3757-67.