Laurent Bonnac, PhD

Summary

Organic synthesis, medicinal chemistry, nucleoside and nucleotide analogues, antiviral strategies.

Research summary/interests

Viruses with pandemic potential such as Dengue, Zika, West Nile, Chikungunya, Ebola, MERS, SARS, new strains of influenza and other emerging viruses, represent significant health threats due to the absence of available treatments.
Developing broad spectrum and inexpensive antiviral drugs will be essential in the face of an outbreak crisis. The Center for Drug Design has been committed to antiviral research since its inception upon the successful development of an anti-HIV drug.

Together with Professor Robert Vince and Professor Robert Geraghty we intend to develop broadly acting antiviral strategies by targeting biological pathways shared by many viruses or by targeting general viral population behaviors.

• Geraghty, Robert J.; Aliota, Matthew T.; Bonnac, Laurent F*. Viruses (2021), 13(4), 667. Broad-spectrum antiviral strategies and nucleoside analogues.
• Soto- Acosta, Ruben; Edwards, Tiffany C.; Dreis, Christine D.; Krishna, Venkatramana D.; Cheeran, Maxim C-J.; Qiu, Li; Xie, Jiashu; Bonnac, Laurent F.*; Geraghty, Robert J. Viruses (2021), 13(12), 2508. Enhancing the Antiviral Potency of Nucleobases for Potential Broad-Spectrum Antiviral Therapies.
• Bonnac Laurent F*; Dreis Christine D; Geraghty Robert J Bioorganic & medicinal chemistry letters (2020), 30(2), 126819.Structure activity relationship, 6-modified purine riboside analogues to activate hSTING, stimulator of interferon genes 
• Qiu Li; Patterson Steven E; Bonnac Laurent F*; Geraghty Robert J.* PLoS neglected tropical diseases (2018), 12(4), e0006421. Nucleobases and corresponding nucleosides display potent antiviral activities against dengue virus possibly through viral lethal mutagenesis
• Rawson JM, Roth ME, Xie J, Daly MB, Clouser CL, Landman SR, Reilly CS, Bonnac Laurent, Kim B, Patterson SE, Mansky LM. Synergistic reduction of HIV-1 infectivity by 5-azacytidine and inhibitors of ribonucleotide reductase. Bioorganic & medicinal chemistry. 2016; 24(11):2410-22.
• Rawson JM, Daly MB, Xie J, Clouser CL, Landman SR, Reilly CS, Bonnac Laurent, Kim B, Patterson SE, Mansky LM. 5-Azacytidine Enhances the Mutagenesis of HIV-1 by Reduction to 5-Aza-2'-Deoxycytidine. Antimicrobial agents and chemotherapy. 2016; 60(4):2318-25.
• Daly MB, Roth ME, Bonnac Laurent, Maldonado JO, Xie J, Clouser CL, Patterson SE, Kim B, Mansky LM. Dual anti-HIV mechanism of clofarabine. Retrovirology. 2016; 13:20.
• Rawson JM, Landman SR, Reilly CS, Bonnac Laurent, Patterson SE, Mansky LM. Lack of mutational hot spots during decitabine-mediated HIV-1 mutagenesis. Antimicrobial agents and chemotherapy. 2015; 59(11):6834-43.
• Clouser CL, Bonnac Laurent, Mansky LM, Patterson SE. Characterization of permeability, stability and anti-HIV-1 activity of decitabine and gemcitabine divalerate prodrugs. Antiviral chemistry & chemotherapy. 2014; 23(6):223-30. NIHMSID: NIHMS699543
• Dapp MJ, Bonnac Laurent, Patterson SE, Mansky LM. Discovery of novel ribonucleoside analogs with activity against human immunodeficiency virus type 1. Journal of virology. 2014; 88(1):354-63.
• Bonnac Laurent, Mansky LM, Patterson SE. Structure-activity relationships and design of viral mutagens and application to lethal mutagenesis. Journal of medicinal chemistry. 2013; 56(23):9403-14.
• Faramarzalian A, McLennan G, Bennett SL, Babsky A, Bansal N, Lieber M, Bonnac Laurent, Pankiewicz K, Jayaram HN. Variability of apoptosis and response in N1-S1 rodent hepatomas to benzamide riboside and correlation to early changes in water apparent diffusion coefficient and sodium MR imaging. Journal of vascular and interventional radiology : JVIR. 2013; 24(6):894-900.
• McLennan G, Bennett SL, Ju S, Babsky A, Bansal N, Shorten ML, Levitin S, Bonnac Laurent, Panciewicz KW, Jayaram HN. Tumor response and apoptosis of N1-S1 rodent hepatomas in response to intra-arterial and intravenous benzamide riboside. Cardiovascular and interventional radiology. 2012; 35(3):645-52.
• Lee SE, Elphick LM, Kramer HB, Jones AM, Child ES, Anderson AA, Bonnac Laurent, Suwaki N, Kessler BM, Gouverneur V, Mann DJ. The chemoselective one-step alkylation and isolation of thiophosphorylated cdk2 substrates in the presence of native cysteine. Chembiochem : a European journal of chemical biology. 2011; 12(4):633-40.
• Bonnac Laurent, Lee SE, Giuffredi GT, Elphick LM, Anderson AA, Child ES, Mann DJ, Gouverneur V. Synthesis and O-phosphorylation of 3,3,4,4-tetrafluoroaryl-C-nucleoside analogues. Organic & biomolecular chemistry. 2010; 8(6):1445-54.
• Elphick LM, Lee SE, Anderson AA, Child ES, Bonnac Laurent, Gouverneur V, Mann DJ. Exploring the roles of protein kinases using chemical genetics. Future medicinal chemistry. 2009; 1(7):1233-41.
• Lee SE, Elphick LM, Anderson AA, Bonnac Laurent, Child ES, Mann DJ, Gouverneur V. Synthesis and reactivity of novel gamma-phosphate modified ATP analogues. Bioorganic & medicinal chemistry letters. 2009; 19(14):3804-7.
• Elphick LM, Lee SE, Child ES, Prasad A, Pignocchi C, Thibaudeau S, Anderson AA, Bonnac Laurent, Gouverneur V, Mann DJ. A quantitative comparison of wild-type and gatekeeper mutant cdk2 for chemical genetic studies with ATP analogues. Chembiochem : a European journal of chemical biology. 2009; 10(9):1519-26.
• Ju S, McLennan G, Bennett SL, Liang Y, Bonnac Laurent, Pankiewicz KW, Jayaram HN. Technical aspects of imaging and transfemoral arterial treatment of N1-S1 tumors in rats: an appropriate model to test the biology and therapeutic response to transarterial treatments of liver cancers. Journal of vascular and interventional radiology : JVIR. 2009; 20(3):410-4.
• Chen L, Petrelli R, Felczak K, Gao G, Bonnac Laurent, Yu JS, Bennett EM, Pankiewicz KW. Nicotinamide adenine dinucleotide based therapeutics. Current medicinal chemistry. 2008; 15(7):650-70.
• Chen L, Gao G, Felczak K, Bonnac Laurent, Patterson SE, Wilson D, Bennett EM, Jayaram HN, Hedstrom L, Pankiewicz KW. Probing binding requirements of type I and type II isoforms of inosine monophosphate dehydrogenase with adenine-modified nicotinamide adenine dinucleotide analogues. Journal of medicinal chemistry. 2007; 50(23):5743-51.
• Bonnac Laurent, Gao GY, Chen L, Felczak K, Bennett EM, Xu H, Kim T, Liu N, Oh H, Tonge PJ, Pankiewicz KW. Synthesis of 4-phenoxybenzamide adenine dinucleotide as NAD analogue with inhibitory activity against enoyl-ACP reductase (InhA) of Mycobacterium tuberculosis. Bioorganic & medicinal chemistry letters. 2007; 17(16):4588-91.
• Chen L, Gao G, Bonnac Laurent, Wilson DJ, Bennett EM, Jayaram HN, Pankiewicz KW. Methylenebis(sulfonamide) linked nicotinamide adenine dinucleotide analogue as an inosine monophosphate dehydrogenase inhibitor. Bioorganic & medicinal chemistry letters. 2007; 17(11):3152-5.
• Suk DH, Bonnac Laurent, Dykstra CC, Pankiewicz KW, Patterson SE. Rational design and synthesis of novel nucleotide anti-Giardia agents. Bioorganic & medicinal chemistry letters. 2007; 17(7):2064-7.
• Bonnac Laurent, Chen L, Pathak R, Gao G, Ming Q, Bennett E, Felczak K, Kullberg M, Patterson SE, Mazzola F, Magni G, Pankiewicz KW. Probing binding requirements of NAD kinase with modified substrate (NAD) analogues. Bioorganic & medicinal chemistry letters. 2007; 17(6):1512-5.
• Bonnac Laurent, Gao GY, Chen L, Patterson SE, Jayaram HN, Pankiewicz KW. Efficient synthesis of benzamide riboside, a potential anticancer agent. Nucleosides, nucleotides & nucleic acids. 2007; 26(10-12):1249-53.
• Chen L, Rejman D, Bonnac Laurent, Pankiewicz KW, Patterson SE. Nucleoside-5'-phosphoimidazolides: reagents for facile synthesis of dinucleoside pyrophosphates. Current protocols in nucleic acid chemistry. 2006; Chapter 13:Unit 13.4.
• Bonnac Laurent, Innocenti A, Winum JY, Casini A, Montero JL, Scozzafava A, Barragan V, Supuran CT. Carbonic anhydrase inhibitors: aliphatic N-phosphorylated sulfamates--a novel zinc-anchoring group leading to nanomolar inhibitors. Journal of enzyme inhibition and medicinal chemistry. 2004; 19(3):275-8.
• Bonnac Laurent, Barragan V, Winum J, Montero J. New pyrophosphate analogues: a facile access to N-(O-alkylsulfamoyl)phosphoramidic acids via a simple and quantitative reaction of N-(O-alkylsulfamoyl)trimethylphospha-?5-azene with bromotrimethylsilane and water Tetrahedron. 2004; 60(10):2187-21900.