Identification of novel small molecule inhibitors against NS2B/NS3 serine protease from Zika virus

Lee, Hyun; Ren, Jinhong; Nocadello, Salvatore; Rice, Amy J.; Ojeda, Isabel; Light, Samuel; Minasov, George; Vargas, Jason; Nagarathnam, Dhanapalan; Anderson, Wayne F.; Johnson, Michael E.

doi:10.1016/j.antiviral.2016.12.016

Identification of novel small molecule inhibitors against NS2B/NS3 serine protease from Zika virus

Journal Article · Mon Dec 26 00:00:00 EST 2016 · Antiviral Research

DOI:https://doi.org/10.1016/j.antiviral.2016.12.016· OSTI ID:1352271

Lee, Hyun ^[1]; Ren, Jinhong ^[2]; Nocadello, Salvatore ^[3]; Rice, Amy J. ^[2]; Ojeda, Isabel ^[2]; Light, Samuel ^[3]; Minasov, George ^[3]; Vargas, Jason ^[2]; Nagarathnam, Dhanapalan ^[4]; Anderson, Wayne F. ^[3]; Johnson, Michael E. ^[1]

Novalex Therapeutics, Inc., Chicago, IL (UnitedStates)
Univ. of Illinois, Chicago, IL (United States)
Northwestern Univ., Chicago, IL (United States). Feinberg School of Medicine
DNSK International, LLC, Hamden, CT (United States)

Zika flavivirus infection during pregnancy appears to produce higher risk of microcephaly, and also causes multiple neurological problems such as Guillain–Barré syndrome. The Zika virus is now widespread in Central and South America, and is anticipated to become an increasing risk in the southern United States. With continuing global travel and the spread of the mosquito vector, the exposure is expected to accelerate, but there are no currently approved treatments against the Zika virus. The Zika NS2B/NS3 protease is an attractive drug target due to its essential role in viral replication. We report our studies have identified several compounds with inhibitory activity (IC₅₀) and binding affinity (K_D) of ~5–10 μM against the Zika NS2B-NS3 protease from testing 71 HCV NS3/NS4A inhibitors that were initially discovered by high-throughput screening of 40,967 compounds. Competition surface plasmon resonance studies and mechanism of inhibition analyses by enzyme kinetics subsequently determined the best compound to be a competitive inhibitor with a $$K_i$$ value of 9.5 μM. We also determined the X-ray structure of the Zika NS2B-NS3 protease in a “pre-open conformation”, a conformation never observed before for any flavivirus proteases. This provides the foundation for new structure-based inhibitor design.

View Accepted Manuscript (DOE)

Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Organization:: National Institute of Allergy and Infectious Diseases (NIAID); National Institutes of Health (NIH); USDOE

OSTI ID:: 1352271

Journal Information:: Antiviral Research, Journal Name: Antiviral Research Journal Issue: C Vol. 139; ISSN 0166-3542

Publisher:: ElsevierCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

References (55)

Development and Characterization of New Peptidomimetic Inhibitors of the West Nile Virus NS2B-NS3 Protease Hammamy, M. Zouhir; Haase, Caroline; Hammami, Maya ChemMedChem, Vol. 8, Issue 2 https://doi.org/10.1002/cmdc.201200497	journal	January 2013
Improved protein-ligand docking using GOLD Verdonk, Marcel L.; Cole, Jason C.; Hartshorn, Michael J. Proteins: Structure, Function, and Bioinformatics, Vol. 52, Issue 4 https://doi.org/10.1002/prot.10465	journal	August 2003
Epik: a software program for pK a prediction and protonation state generation for drug-like molecules Shelley, John C.; Cholleti, Anuradha; Frye, Leah L. Journal of Computer-Aided Molecular Design, Vol. 21, Issue 12 https://doi.org/10.1007/s10822-007-9133-z	journal	September 2007
Structural and mutational analysis of the interaction between the Middle-East respiratory syndrome coronavirus (MERS-CoV) papain-like protease and human ubiquitin Lei, Jian; Hilgenfeld, Rolf Virologica Sinica, Vol. 31, Issue 4 https://doi.org/10.1007/s12250-016-3742-4	journal	May 2016
Structural basis of Zika virus helicase in recognizing its substrates Tian, Hongliang; Ji, Xiaoyun; Yang, Xiaoyun Protein & Cell, Vol. 7, Issue 8 https://doi.org/10.1007/s13238-016-0293-2	journal	July 2016
Zika Virus (I). Isolations and serological specificity Dick, G. W. A.; Kitchen, S. F.; Haddow, A. J. Transactions of the Royal Society of Tropical Medicine and Hygiene, Vol. 46, Issue 5 https://doi.org/10.1016/0035-9203(52)90042-4	journal	September 1952
[20] Processing of X-ray diffraction data collected in oscillation mode Otwinowski, Zbyszek; Minor, Wladek Macromolecular Crystallography Part A, 307-326 https://doi.org/10.1016/S0076-6879(97)76066-X	book	January 1997
Pathogenic flaviviruses Gould, Ea; Solomon, T. The Lancet, Vol. 371, Issue 9611 https://doi.org/10.1016/S0140-6736(08)60238-X	journal	February 2008
Zika virus and Guillain-Barré syndrome: another viral cause to add to the list Smith, David W.; Mackenzie, John The Lancet, Vol. 387, Issue 10027 https://doi.org/10.1016/S0140-6736(16)00564-X	journal	April 2016
Molecular targets for flavivirus drug discovery Sampath, Aruna; Padmanabhan, R. Antiviral Research, Vol. 81, Issue 1 https://doi.org/10.1016/j.antiviral.2008.08.004	journal	January 2009
Anthracene-based inhibitors of dengue virus NS2B–NS3 protease☆ Tomlinson, Suzanne M.; Watowich, Stanley J. Antiviral Research, Vol. 89, Issue 2 https://doi.org/10.1016/j.antiviral.2010.12.006	journal	February 2011
Structural biology of dengue virus enzymes: Towards rational design of therapeutics Noble, Christian G.; Shi, Pei-Yong Antiviral Research, Vol. 96, Issue 2 https://doi.org/10.1016/j.antiviral.2012.09.007	journal	November 2012
Characterization of 8-hydroxyquinoline derivatives containing aminobenzothiazole as inhibitors of dengue virus type 2 protease in vitro Lai, Huiguo; Sridhar Prasad, G.; Padmanabhan, Radhakrishnan Antiviral Research, Vol. 97, Issue 1 https://doi.org/10.1016/j.antiviral.2012.10.009	journal	January 2013
Ten years of dengue drug discovery: Progress and prospects Lim, Siew Pheng; Wang, Qing-Yin; Noble, Christian G. Antiviral Research, Vol. 100, Issue 2 https://doi.org/10.1016/j.antiviral.2013.09.013	journal	November 2013
Antiviral activities of 15 dengue NS2B-NS3 protease inhibitors using a human cell-based viral quantification assay Chu, Justin Jang Hann; Lee, Regina Ching Hua; Ang, Melgious Jin Yan Antiviral Research, Vol. 118 https://doi.org/10.1016/j.antiviral.2015.03.010	journal	June 2015
The flavivirus NS2B–NS3 protease–helicase as a target for antiviral drug development Luo, Dahai; Vasudevan, Subhash G.; Lescar, Julien Antiviral Research, Vol. 118 https://doi.org/10.1016/j.antiviral.2015.03.014	journal	June 2015
Zika virus: History, emergence, biology, and prospects for control Weaver, Scott C.; Costa, Federico; Garcia-Blanco, Mariano A. Antiviral Research, Vol. 130 https://doi.org/10.1016/j.antiviral.2016.03.010	journal	June 2016
Design and evaluation of substrate-based octapeptide and non substrate-based tetrapeptide inhibitors of dengue virus NS2B–NS3 proteases Prusis, Peteris; Junaid, Muhammad; Petrovska, Ramona Biochemical and Biophysical Research Communications, Vol. 434, Issue 4 https://doi.org/10.1016/j.bbrc.2013.03.139	journal	May 2013
Design, synthesis and characterization of novel 1,2-benzisothiazol-3(2H)-one and 1,3,4-oxadiazole hybrid derivatives: Potent inhibitors of Dengue and West Nile virus NS2B/NS3 proteases Lai, Huiguo; Dou, Dengfeng; Aravapalli, Sridhar Bioorganic & Medicinal Chemistry, Vol. 21, Issue 1 https://doi.org/10.1016/j.bmc.2012.10.058	journal	January 2013
Identification of novel thiadiazoloacrylamide analogues as inhibitors of dengue-2 virus NS2B/NS3 protease Liu, Hailong; Wu, Ruoming; Sun, Yanyan Bioorganic & Medicinal Chemistry, Vol. 22, Issue 22 https://doi.org/10.1016/j.bmc.2014.09.057	journal	November 2014
Discovery and SAR studies of methionine–proline anilides as dengue virus NS2B-NS3 protease inhibitors Zhou, Guo-Chun; Weng, Zhibing; Shao, Xiaoxia Bioorganic & Medicinal Chemistry Letters, Vol. 23, Issue 24 https://doi.org/10.1016/j.bmcl.2013.10.071	journal	December 2013
A perspective on targeting non-structural proteins to combat neglected tropical diseases: Dengue, West Nile and Chikungunya viruses Bhakat, Soumendranath; Karubiu, Wilson; Jayaprakash, Venkatesan European Journal of Medicinal Chemistry, Vol. 87 https://doi.org/10.1016/j.ejmech.2014.10.010	journal	November 2014
Discovery of antiviral molecules for dengue: In silico search and biological evaluation Cabarcas-Montalvo, Maria; Maldonado-Rojas, Wilson; Montes-Grajales, Diana European Journal of Medicinal Chemistry, Vol. 110 https://doi.org/10.1016/j.ejmech.2015.12.030	journal	March 2016
Hepatitis C virus resistance to protease inhibitors Halfon, Philippe; Locarnini, Stephen Journal of Hepatology, Vol. 55, Issue 1 https://doi.org/10.1016/j.jhep.2011.01.011	journal	July 2011
Zika fever and congenital Zika syndrome: An unexpected emerging arboviral disease Chan, Jasper F. W.; Choi, Garnet K. Y.; Yip, Cyril C. Y. Journal of Infection, Vol. 72, Issue 5 https://doi.org/10.1016/j.jinf.2016.02.011	journal	May 2016
Structure of West Nile Virus NS3 Protease: Ligand Stabilization of the Catalytic Conformation Robin, Gautier; Chappell, Keith; Stoermer, Martin J. Journal of Molecular Biology, Vol. 385, Issue 5 https://doi.org/10.1016/j.jmb.2008.11.026	journal	February 2009
Expression Analysis Highlights AXL as a Candidate Zika Virus Entry Receptor in Neural Stem Cells Nowakowski, Tomasz J.; Pollen, Alex A.; Di Lullo, Elizabeth Cell Stem Cell, Vol. 18, Issue 5 https://doi.org/10.1016/j.stem.2016.03.012	journal	May 2016
Identification of a Novel Inhibitor of Dengue Virus Protease through Use of a Virtual Screening Drug Discovery Web Portal Viswanathan, Usha; Tomlinson, Suzanne M.; Fonner, John M. Journal of Chemical Information and Modeling, Vol. 54, Issue 10 https://doi.org/10.1021/ci500531r	journal	September 2014
Discovery of Novel Small Molecule Inhibitors of Dengue Viral NS2B-NS3 Protease Using Virtual Screening and Scaffold Hopping Deng, Jing; Li, Ning; Liu, Hongchuan Journal of Medicinal Chemistry, Vol. 55, Issue 14 https://doi.org/10.1021/jm300146f	journal	July 2012
Critical Effect of Peptide Cyclization on the Potency of Peptide Inhibitors against Dengue Virus NS2B-NS3 Protease Xu, Shaoqiong; Li, Hua; Shao, Xiaoxia Journal of Medicinal Chemistry, Vol. 55, Issue 15 https://doi.org/10.1021/jm300655h	journal	July 2012
Mechanisms of activation and inhibition of Zika virus NS2B-NS3 protease Chen, Xia; Yang, Kailin; Wu, Chen Cell Research, Vol. 26, Issue 11 https://doi.org/10.1038/cr.2016.116	journal	October 2016
Structure of the NS2B-NS3 protease from Zika virus after self-cleavage Phoo, Wint Wint; Li, Yan; Zhang, Zhenzhen Nature Communications, Vol. 7, Issue 1 https://doi.org/10.1038/ncomms13410	journal	November 2016
Structural basis for the activation of flaviviral NS3 proteases from dengue and West Nile virus Erbel, Paul; Schiering, Nikolaus; D'Arcy, Allan Nature Structural & Molecular Biology, Vol. 13, Issue 4 https://doi.org/10.1038/nsmb1073	journal	March 2006
Drug resistance against HCV NS3/4A inhibitors is defined by the balance of substrate recognition versus inhibitor binding Romano, K. P.; Ali, A.; Royer, W. E. Proceedings of the National Academy of Sciences, Vol. 107, Issue 49 https://doi.org/10.1073/pnas.1006370107	journal	November 2010
Zika virus: a previously slow pandemic spreads rapidly through the Americas Gatherer, Derek; Kohl, Alain Journal of General Virology, Vol. 97, Issue 2 https://doi.org/10.1099/jgv.0.000381	journal	February 2016
Coot model-building tools for molecular graphics Emsley, Paul; Cowtan, Kevin Acta Crystallographica Section D Biological Crystallography, Vol. 60, Issue 12, p. 2126-2132 https://doi.org/10.1107/S0907444904019158	journal	November 2004
REFMAC 5 for the refinement of macromolecular crystal structures Murshudov, Garib N.; Skubák, Pavol; Lebedev, Andrey A. Acta Crystallographica Section D Biological Crystallography, Vol. 67, Issue 4 https://doi.org/10.1107/S0907444911001314	journal	March 2011
Structural evidence for regulation and specificity of flaviviral proteases and evolution of the Flaviviridae fold Aleshin, Alexander E.; Shiryaev, Sergey A.; Strongin, Alex Y. Protein Science, Vol. 16, Issue 5 https://doi.org/10.1110/ps.072753207	journal	May 2007
Structure-guided Discovery of a Novel Non-peptide Inhibitor of Dengue Virus NS2B-NS3 Protease Li, Linfeng; Basavannacharya, Chandrakala; Chan, Kitti Wing Ki Chemical Biology & Drug Design, Vol. 86, Issue 3 https://doi.org/10.1111/cbdd.12500	journal	February 2015
The race for a Zika vaccine is on Cohen, J. Science, Vol. 351, Issue 6273 https://doi.org/10.1126/science.351.6273.543	journal	February 2016
Evidence grows for Zika virus as pregnancy danger Vogel, Gretchen Science, Vol. 351, Issue 6278 https://doi.org/10.1126/science.351.6278.1123	journal	March 2016
The 3.8 A resolution cryo-EM structure of Zika virus Sirohi, D.; Chen, Z.; Sun, L. Science, Vol. 352, Issue 6284 https://doi.org/10.1126/science.aaf5316	journal	March 2016
Crystal structure of Zika virus NS2B-NS3 protease in complex with a boronate inhibitor Lei, Jian; Hansen, Guido; Nitsche, Christoph Science, Vol. 353, Issue 6298 https://doi.org/10.1126/science.aag2419	journal	July 2016
Novel Dengue Virus-Specific NS2B/NS3 Protease Inhibitor, BP2109, Discovered by a High-Throughput Screening Assay Yang, Chi-Chen; Hsieh, Yi-Chen; Lee, Shiow-Ju Antimicrobial Agents and Chemotherapy, Vol. 55, Issue 1 https://doi.org/10.1128/AAC.00855-10	journal	October 2010
A Novel Dengue Virus Inhibitor, BP13944, Discovered by High-Throughput Screening with Dengue Virus Replicon Cells Selects for Resistance in the Viral NS2B/NS3 Protease Yang, Chi-Chen; Hu, Han-Shu; Wu, Ren-Huang Antimicrobial Agents and Chemotherapy, Vol. 58, Issue 1 https://doi.org/10.1128/AAC.01281-13	journal	October 2013
Novel Dengue Virus NS2B/NS3 Protease Inhibitors Wu, Hongmei; Bock, Stefanie; Snitko, Mariya Antimicrobial Agents and Chemotherapy, Vol. 59, Issue 2 https://doi.org/10.1128/AAC.03543-14	journal	December 2014
Ligand-Bound Structures of the Dengue Virus Protease Reveal the Active Conformation Noble, C. G.; Seh, C. C.; Chao, A. T. Journal of Virology, Vol. 86, Issue 1 https://doi.org/10.1128/JVI.06225-11	journal	October 2011
Phylogeny of the Genus Flavivirus Kuno, Goro; Chang, Gwong-Jen J.; Tsuchiya, K. Richard Journal of Virology, Vol. 72, Issue 1 https://doi.org/10.1128/JVI.72.1.73-83.1998	journal	January 1998
Molecular Evolution of Zika Virus during Its Emergence in the 20th Century Faye, Oumar; Freire, Caio C. M.; Iamarino, Atila PLoS Neglected Tropical Diseases, Vol. 8, Issue 1 https://doi.org/10.1371/journal.pntd.0002636	journal	January 2014
Zika Virus: Medical Countermeasure Development Challenges Malone, Robert W.; Homan, Jane; Callahan, Michael V. PLOS Neglected Tropical Diseases, Vol. 10, Issue 3 https://doi.org/10.1371/journal.pntd.0004530	journal	March 2016
High-Throughput Screening (HTS) and Hit Validation to Identify Small Molecule Inhibitors with Activity against NS3/4A proteases from Multiple Hepatitis C Virus Genotypes Lee, Hyun; Zhu, Tian; Patel, Kavankumar PLoS ONE, Vol. 8, Issue 10 https://doi.org/10.1371/journal.pone.0075144	journal	October 2013
DENV Inhibits Type I IFN Production in Infected Cells by Cleaving Human STING Aguirre, Sebastian; Maestre, Ana M.; Pagni, Sarah PLoS Pathogens, Vol. 8, Issue 10 https://doi.org/10.1371/journal.ppat.1002934	journal	October 2012
History, Epidemiology, and Clinical Manifestations of Zika: A Systematic Review Paixão, Enny S.; Barreto, Florisneide; da Glória Teixeira, Maria American Journal of Public Health, Vol. 106, Issue 4 https://doi.org/10.2105/AJPH.2016.303112	journal	April 2016
Initial Description of the Presumed Congenital Zika Syndrome Miranda-Filho, Demócrito de Barros; Martelli, Celina Maria Turchi; Ximenes, Ricardo Arraes de Alencar American Journal of Public Health, Vol. 106, Issue 4 https://doi.org/10.2105/AJPH.2016.303115	journal	April 2016
Structural Genomics and Drug Discovery for Infectious Diseases Anderson, W. Infectious Disorders - Drug Targets, Vol. 9, Issue 5 https://doi.org/10.2174/187152609789105713	journal	October 2009

Cited By (25)

Development of small-molecule viral inhibitors targeting various stages of the life cycle of emerging and re-emerging viruses Wang, Xiaohuan; Zou, Peng; Wu, Fan Frontiers of Medicine, Vol. 11, Issue 4 https://doi.org/10.1007/s11684-017-0589-5	journal	November 2017
Hydroxychloroquine Inhibits Zika Virus NS2B-NS3 Protease Kumar, Ankur; Liang, Brooke; Aarthy, Murali ACS Omega, Vol. 3, Issue 12 https://doi.org/10.1021/acsomega.8b01002	journal	December 2018
Male germ cells support long-term propagation of Zika virus Robinson, Christopher L.; Chong, Angie C. N.; Ashbrook, Alison W. Nature Communications, Vol. 9, Issue 1 https://doi.org/10.1038/s41467-018-04444-w	journal	May 2018
Zika Virus Targeting by Screening Inhibitors against NS2B/NS3 Protease Choudhry, Hani; Alzahrani, Faisal A.; Hassan, Mohammed A. BioMed Research International, Vol. 2019 https://doi.org/10.1155/2019/3947245	journal	November 2019
Allostery in the dengue virus NS3 helicase: Insights into the NTPase cycle from molecular simulations Davidson, Russell B.; Hendrix, Josie; Geiss, Brian J. PLOS Computational Biology, Vol. 14, Issue 4 https://doi.org/10.1371/journal.pcbi.1006103	journal	April 2018
Advances in Developing Therapies to Combat Zika Virus: Current Knowledge and Future Perspectives Munjal, Ashok; Khandia, Rekha; Dhama, Kuldeep Frontiers in Microbiology, Vol. 8 https://doi.org/10.3389/fmicb.2017.01469	journal	August 2017
Zika Virus: What Have We Learnt Since the Start of the Recent Epidemic? Saiz, Juan-Carlos; Martín-Acebes, Miguel A.; Bueno-Marí, Rubén Frontiers in Microbiology, Vol. 8 https://doi.org/10.3389/fmicb.2017.01554	journal	August 2017
Development of Small-Molecule Inhibitors Against Zika Virus Infection Wang, Lili; Liang, Ruiying; Gao, Yaning Frontiers in Microbiology, Vol. 10 https://doi.org/10.3389/fmicb.2019.02725	journal	December 2019
Discovery of Novel Druggable Sites on Zika Virus NS3 Helicase Using X-ray Crystallography-Based Fragment Screening Munawar, Ali; Beelen, Steven; Munawar, Ahmad International Journal of Molecular Sciences, Vol. 19, Issue 11 https://doi.org/10.3390/ijms19113664	journal	November 2018
Discovery and Computational Analyses of Novel Small Molecule Zika Virus Inhibitors Zhu, Siyu; Zhang, Chaozai; Huang, Lina S. Molecules, Vol. 24, Issue 8 https://doi.org/10.3390/molecules24081465	journal	April 2019
Antiviral Agents in Development for Zika Virus Infections No authors listed Pharmaceuticals, Vol. 12, Issue 3 https://doi.org/10.3390/ph12030101	journal	June 2019
Therapeutic Advances Against ZIKV: A Quick Response, a Long Way to Go Saiz, Juan-Carlos Pharmaceuticals, Vol. 12, Issue 3 https://doi.org/10.3390/ph12030127	journal	August 2019
Probing Molecular Insights into Zika Virus–Host Interactions Lee, Ina; Bos, Sandra; Li, Ge Viruses, Vol. 10, Issue 5 https://doi.org/10.3390/v10050233	journal	May 2018
Design, Synthesis and Discovery of N,N’ ‐Carbazoyl‐aryl‐urea Inhibitors of Zika NS5 Methyltransferase and Virus Replication Spizzichino, Sharon; Mattedi, Giulio; Lauder, Kate ChemMedChem, Vol. 15, Issue 4 https://doi.org/10.1002/cmdc.201900533	journal	February 2020
MD simulations reveal alternate conformations of the oxyanion hole in the Zika virus NS2B/NS3 protease Ren, Jinhong; Lee, Hyun; Kotak, Alpa Proteins: Structure, Function, and Bioinformatics, Vol. 88, Issue 2 https://doi.org/10.1002/prot.25809	journal	September 2019
Carnosine exhibits significant antiviral activity against Dengue and Zika virus Rothan, Hussin A.; Abdulrahman, Ammar Yasir; Khazali, Ahmad Suhail Journal of Peptide Science, Vol. 25, Issue 8 https://doi.org/10.1002/psc.3196	journal	July 2019
High Throughput and Computational Repurposing for Neglected Diseases Hernandez, Helen W.; Soeung, Melinda; Zorn, Kimberley M. Pharmaceutical Research, Vol. 36, Issue 2 https://doi.org/10.1007/s11095-018-2558-3	journal	December 2018
RNA-Dependent Structures of the RNA-Binding Loop in the Flavivirus NS3 Helicase Davidson, Russell B.; Hendrix, Josie; Geiss, Brian J. The Journal of Physical Chemistry B, Vol. 124, Issue 12 https://doi.org/10.1021/acs.jpcb.0c00457	journal	February 2020
Structural biology of Zika virus and other flaviviruses Hasan, S. Saif; Sevvana, Madhumati; Kuhn, Richard J. Nature Structural & Molecular Biology, Vol. 25, Issue 1 https://doi.org/10.1038/s41594-017-0010-8	journal	January 2018
Small neutral Gd( iii ) tags for distance measurements in proteins by double electron–electron resonance experiments Mahawaththa, Mithun C.; Lee, Michael D.; Giannoulis, Angeliki Physical Chemistry Chemical Physics, Vol. 20, Issue 36 https://doi.org/10.1039/c8cp03532f	journal	January 2018
Identification of a C2-symmetric diol based human immunodeficiency virus protease inhibitor targeting Zika virus NS2B-NS3 protease Akaberi, Dario; Chinthakindi, Praveen K.; Båhlström, Amanda Journal of Biomolecular Structure and Dynamics, Vol. 38, Issue 18 https://doi.org/10.1080/07391102.2019.1704882	journal	December 2019
Nonhuman Primate Models of Zika Virus Infection, Immunity, and Therapeutic Development Osuna, Christa E.; Whitney, James B. The Journal of Infectious Diseases, Vol. 216, Issue suppl_10 https://doi.org/10.1093/infdis/jix540	journal	December 2017
Cathelicidin-Derived Antimicrobial Peptides Inhibit Zika Virus Through Direct Inactivation and Interferon Pathway He, Miao; Zhang, Hainan; Li, Yuju Frontiers in Immunology, Vol. 9 https://doi.org/10.3389/fimmu.2018.00722	journal	April 2018
Natural Products from Cyanobacteria: Focus on Beneficial Activities Demay, Justine; Bernard, Cécile; Reinhardt, Anita Marine Drugs, Vol. 17, Issue 6 https://doi.org/10.3390/md17060320	journal	May 2019
Identification of a C2-symmetric diol based human immunodeficiency virus protease inhibitor targeting Zika virus NS2B-NS3 protease Akaberi, Dario; Chinthakindi, Praveen K.; Båhlström, Amanda Taylor & Francis https://doi.org/10.6084/m9.figshare.11467308.v1	text	January 2019

Similar Records

Discovery, X-ray Crystallography and Antiviral Activity of Allosteric Inhibitors of Flavivirus NS2B-NS3 Protease

Journal Article · Mon Apr 22 20:00:00 EDT 2019 · Journal of the American Chemical Society · OSTI ID:1561316

Characterization of molecular interactions between Zika virus protease and peptides derived from the C-terminus of NS2B

Journal Article · Sat Sep 15 00:00:00 EDT 2018 · Biochemical and Biophysical Research Communications · OSTI ID:23136903

Purification and crystallization of dengue and West Nile virus NS2B–NS3 complexes

Journal Article · Tue Jan 31 23:00:00 EST 2006 · Acta Crystallographica. Section F · OSTI ID:22356260

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
60 APPLIED LIFE SCIENCES
NS2B/NS3 serine protease
Small molecule inhibitor
Zika flavivirus
apo ZIKV NS2B-NS3pro structure

Identification of novel small molecule inhibitors against NS2B/NS3 serine protease from Zika virus

Citation Formats

References (55)

Cited By (25)

Similar Records

Related Subjects