FREE SHIPPING over $40
OVER 10000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Viruses2023; 15(2); 413; doi: 10.3390/v15020413

Advances in the Development of Small Molecule Antivirals against Equine Encephalitic Viruses.

Abstract: Venezuelan, western, and eastern equine encephalitic alphaviruses (VEEV, WEEV, and EEEV, respectively) are arboviruses that are highly pathogenic to equines and cause significant harm to infected humans. Currently, human alphavirus infection and the resulting diseases caused by them are unmitigated due to the absence of approved vaccines or therapeutics for general use. These circumstances, combined with the unpredictability of outbreaks-as exemplified by a 2019 EEE surge in the United States that claimed 19 patient lives-emphasize the risks posed by these viruses, especially for aerosolized VEEV and EEEV which are potential biothreats. Herein, small molecule inhibitors of VEEV, WEEV, and EEEV are reviewed that have been identified or advanced in the last five years since a comprehensive review was last performed. We organize structures according to host- versus virus-targeted mechanisms, highlight cellular and animal data that are milestones in the development pipeline, and provide a perspective on key considerations for the progression of compounds at early and later stages of advancement.
Get Full Text
Publication Date: 2023-02-01 PubMed ID: 36851628PubMed Central: PMC9958955DOI: 10.3390/v15020413Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
LinkedInCopy
  • Journal Article
  • Review
  • Research Support
  • N.I.H.
  • Extramural

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research article discusses recent advancements in the development of small molecule antivirals against the highly pathogenic equine encephalitic alphaviruses, for which currently there are no approved vaccines or therapeutics available.

Context and Background

  • The article addresses the high pathogenicity of equine encephalitic alphaviruses (including Venezuelan, western, and eastern variants), and how they cause significant harm to both equines and humans.
  • Currently, there are no approved therapies or vaccines for the treatment of human alphavirus infection, and this lack of medical preparation adds to the unpredictable and dangerous nature of outbreaks.
  • The authors mention an occurrence from 2019 where a surge in the eastern equine encephalitis virus (EEEV) in the United States led to the loss of 19 lives, further emphasizing the need for focused therapeutic research.

  • Specifically, the study pinpoints aerosolized Venezuelan and eastern equine encephalitic viruses as potential biothreats.

Objective and Methodology

  • The research article is essentially a detailed review dedicated to small molecule inhibitors that have been identified or developed against VEEV, WEEV, and EEEV in the past five years. This is framed as a timely update since the last comprehensive review.
  • The six-year period preceding the writing of this article is the focus mainly, as this is when significant advancements were made in relation to small molecular inhibitors.
  • The molecule structures are organized on the basis of whether they target host or virus mechanism—into host-targeted and virus-targeted mechanisms respectively.

Findings and Perspective

  • The review article highlights significant findings from cellular and animal data that mark key steps forward in the development process.
  • The authors also provide insights into the key considerations for the progression of compounds at early and later stages of advancement.
  • The path forward, according to the authors, is through continued research and development of antivirals against these alphaviruses, with the keep parameters being the considerations for progression at different stages of the research.

Cite This Article

APA
Ogorek TJ, Golden JE. (2023). Advances in the Development of Small Molecule Antivirals against Equine Encephalitic Viruses. Viruses, 15(2), 413. https://doi.org/10.3390/v15020413

Publication

Viruses
ISSN: 1999-4915
NlmUniqueID: 101509722
Country: Switzerland
Language: English
Volume: 15
Issue: 2
PII: 413

Researcher Affiliations

Ogorek, Tyler J
  • Department of Chemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
Golden, Jennifer E
  • Department of Chemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
  • Division of Pharmaceutical Sciences, School of Pharmacy, University of Wisconsin-Madison, Madison, WI 53705, USA.

MeSH Terms

  • Animals
  • Horses
  • Humans
  • Antiviral Agents / pharmacology
  • Antiviral Agents / therapeutic use
  • Encephalomyelitis, Equine / drug therapy
  • Alphavirus
  • Disease Outbreaks
  • Venezuela

Grant Funding

  • U19 AI142762 / NIAID NIH HHS

Conflict of Interest Statement

J.E.G. is a co-inventor of ML336, BDGR-4, BDGR-5, BDGR-69-70, and compounds 7a, 7b, and 7o which are included in this review.

References

This article includes 193 references
  1. Zacks MA, Paessler S. Encephalitic alphaviruses.. Vet Microbiol 2010 Jan 27;140(3-4):281-6.
    doi: 10.1016/j.vetmic.2009.08.023pmc: PMC2814892pubmed: 19775836google scholar: lookup
  2. Johnson KM, Martin DH. Venezuelan equine encephalitis.. Adv Vet Sci Comp Med 1974;18(0):79-116.
    pubmed: 4609399
  3. Suhrbier A, Jaffar-Bandjee MC, Gasque P. Arthritogenic alphaviruses--an overview.. Nat Rev Rheumatol 2012 May 8;8(7):420-9.
    doi: 10.1038/nrrheum.2012.64pubmed: 22565316google scholar: lookup
  4. Chen W, Foo SS, Sims NA, Herrero LJ, Walsh NC, Mahalingam S. Arthritogenic alphaviruses: new insights into arthritis and bone pathology.. Trends Microbiol 2015 Jan;23(1):35-43.
    doi: 10.1016/j.tim.2014.09.005pubmed: 25449049google scholar: lookup
  5. Forrester NL, Wertheim JO, Dugan VG, Auguste AJ, Lin D, Adams AP, Chen R, Gorchakov R, Leal G, Estrada-Franco JG, Pandya J, Halpin RA, Hari K, Jain R, Stockwell TB, Das SR, Wentworth DE, Smith MD, Kosakovsky Pond SL, Weaver SC. Evolution and spread of Venezuelan equine encephalitis complex alphavirus in the Americas.. PLoS Negl Trop Dis 2017 Aug;11(8):e0005693.
    doi: 10.1371/journal.pntd.0005693pmc: PMC5557581pubmed: 28771475google scholar: lookup
  6. Aguilar PV, Estrada-Franco JG, Navarro-Lopez R, Ferro C, Haddow AD, Weaver SC. Endemic Venezuelan equine encephalitis in the Americas: hidden under the dengue umbrella.. Future Virol 2011;6(6):721-740.
    doi: 10.2217/fvl.11.50pmc: PMC3134406pubmed: 21765860google scholar: lookup
  7. Guzmán-Terán C, Calderón-Rangel A, Rodriguez-Morales A, Mattar S. Venezuelan equine encephalitis virus: the problem is not over for tropical America.. Ann Clin Microbiol Antimicrob 2020 May 19;19(1):19.
    doi: 10.1186/s12941-020-00360-4pmc: PMC7236962pubmed: 32429942google scholar: lookup
  8. Phelps AL, O'Brien LM, Eastaugh LS, Davies C, Lever MS, Ennis J, Zeitlin L, Nunez A, Ulaeto DO. Susceptibility and Lethality of Western Equine Encephalitis Virus in Balb/c Mice When Infected by the Aerosol Route.. Viruses 2017 Jun 27;9(7).
    doi: 10.3390/v9070163pmc: PMC5537655pubmed: 28654007google scholar: lookup
  9. Reisen W.K.. Western Equine Encephalomyelitis. In: Monath T.P., editor. The Arboviruses. 1st ed. Volume 5. CRC Press; Boca Raton, FL, USA: 1988. pp. 89–137.
  10. Calisher CH. Medically important arboviruses of the United States and Canada.. Clin Microbiol Rev 1994 Jan;7(1):89-116.
    doi: 10.1128/CMR.7.1.89pmc: PMC358307pubmed: 8118792google scholar: lookup
  11. Millet N, Faiek S, Gurrieri D, Kals K, Adams W, Hamaty E, Trivedi M, Zeidwerg D. Deadly Neuroinvasive Mosquito-Borne Virus: A Case of Eastern Equine Encephalitis.. Perm J 2021 May;25.
    doi: 10.7812/TPP/20.288pmc: PMC8784058pubmed: 33970094google scholar: lookup
  12. Lindsey NP, Martin SW, Staples JE, Fischer M. Notes from the Field: Multistate Outbreak of Eastern Equine Encephalitis Virus - United States, 2019.. MMWR Morb Mortal Wkly Rep 2020 Jan 17;69(2):50-51.
    doi: 10.15585/mmwr.mm6902a4pmc: PMC6973353pubmed: 31945032google scholar: lookup
  13. Centers for Disease Control and Prevention | Eastern Equine Encephalitis. [(accessed on 1 December 2022)]; Available online: https://www.cdc.gov/easternequineencephalitis/statistics-maps/index.html.
  14. Ronca SE, Dineley KT, Paessler S. Neurological Sequelae Resulting from Encephalitic Alphavirus Infection.. Front Microbiol 2016;7:959.
    doi: 10.3389/fmicb.2016.00959pmc: PMC4913092pubmed: 27379085google scholar: lookup
  15. Bowen GS, Fashinell TR, Dean PB, Gregg MB. Clinical aspects of human Venezuelan equine encephalitis in Texas.. Bull Pan Am Health Organ 1976;10(1):46-57.
    pubmed: 949558
  16. Hayes E.B., Staples J.E. Principles and Practice of Pediatric Infectious Diseases. 4th ed. Elsevier; London, UK: 2012. pp. 1097–1099.
  17. Reichert E, Clase A, Bacetty A, Larsen J. Alphavirus antiviral drug development: scientific gap analysis and prospective research areas.. Biosecur Bioterror 2009 Dec;7(4):413-27.
    doi: 10.1089/bsp.2009.0032pubmed: 20028250google scholar: lookup
  18. Sidwell RW, Smee DF. Viruses of the Bunya- and Togaviridae families: potential as bioterrorism agents and means of control.. Antiviral Res 2003 Jan;57(1-2):101-11.
    doi: 10.1016/S0166-3542(02)00203-6pubmed: 12615306google scholar: lookup
  19. Christopher GW, Cieslak TJ, Pavlin JA, Eitzen EM Jr. Biological warfare. A historical perspective.. JAMA 1997 Aug 6;278(5):412-7.
    doi: 10.1001/jama.1997.03550050074036pubmed: 9244333google scholar: lookup
  20. Alevizatos AC, McKinney RW, Feigin RD. Live, attenuated Venezuelan equine encephalomyelitis virus vaccine. I. Clinical effects in man.. Am J Trop Med Hyg 1967 Nov;16(6):762-8.
    doi: 10.4269/ajtmh.1967.16.762pubmed: 6066224google scholar: lookup
  21. Pittman PR, Makuch RS, Mangiafico JA, Cannon TL, Gibbs PH, Peters CJ. Long-term duration of detectable neutralizing antibodies after administration of live-attenuated VEE vaccine and following booster vaccination with inactivated VEE vaccine.. Vaccine 1996 Mar;14(4):337-43.
    doi: 10.1016/0264-410X(95)00168-Zpubmed: 8744562google scholar: lookup
  22. Centers for Disease Control and Prevention | Treatment & Prevention | Eastern Equine Encephalitis. [(accessed on 2 October 2022)]; Available online: https://www.cdc.gov/easternequineencephalitis/healthcare-providers/treatment-prevention.html.
  23. Stromberg ZR, Fischer W, Bradfute SB, Kubicek-Sutherland JZ, Hraber P. Vaccine Advances against Venezuelan, Eastern, and Western Equine Encephalitis Viruses.. Vaccines (Basel) 2020 Jun 3;8(2).
    doi: 10.3390/vaccines8020273pmc: PMC7350001pubmed: 32503232google scholar: lookup
  24. Paessler S, Weaver SC. Vaccines for Venezuelan equine encephalitis.. Vaccine 2009 Nov 5;27 Suppl 4:D80-5.
    doi: 10.1016/j.vaccine.2009.07.095pmc: PMC2764542pubmed: 19837294google scholar: lookup
  25. Powers AM. Resurgence of Interest in Eastern Equine Encephalitis Virus Vaccine Development.. J Med Entomol 2022 Jan 12;59(1):20-26.
    doi: 10.1093/jme/tjab135pubmed: 34734632google scholar: lookup
  26. Burke CW, Froude JW, Rossi F, White CE, Moyer CL, Ennis J, Pitt ML, Streatfield S, Jones RM, Musiychuk K, Kervinen J, Zeitlin L, Yusibov V, Glass PJ. Therapeutic monoclonal antibody treatment protects nonhuman primates from severe Venezuelan equine encephalitis virus disease after aerosol exposure.. PLoS Pathog 2019 Dec;15(12):e1008157.
    doi: 10.1371/journal.ppat.1008157pmc: PMC6907853pubmed: 31790515google scholar: lookup
  27. Williamson LE, Gilliland T Jr, Yadav PK, Binshtein E, Bombardi R, Kose N, Nargi RS, Sutton RE, Durie CL, Armstrong E, Carnahan RH, Walker LM, Kim AS, Fox JM, Diamond MS, Ohi MD, Klimstra WB, Crowe JE Jr. Human Antibodies Protect against Aerosolized Eastern Equine Encephalitis Virus Infection.. Cell 2020 Dec 23;183(7):1884-1900.e23.
    doi: 10.1016/j.cell.2020.11.011pmc: PMC7806206pubmed: 33301709google scholar: lookup
  28. Kim AS, Austin SK, Gardner CL, Zuiani A, Reed DS, Trobaugh DW, Sun C, Basore K, Williamson LE, Crowe JE Jr, Slifka MK, Fremont DH, Klimstra WB, Diamond MS. Protective antibodies against Eastern equine encephalitis virus bind to epitopes in domains A and B of the E2 glycoprotein.. Nat Microbiol 2019 Jan;4(1):187-197.
    doi: 10.1038/s41564-018-0286-4pmc: PMC6294662pubmed: 30455470google scholar: lookup
  29. ChemicalProbes.Org. Chemical Probes | Information Centre | Probes Criteria. [(accessed on 31 January 2023)]. Available online: https://www.chemicalprobes.org/information-centre#probes-criteria.
  30. Antolin AA, Sanfelice D, Crisp A, Villasclaras Fernandez E, Mica IL, Chen Y, Collins I, Edwards A, Müller S, Al-Lazikani B, Workman P. The Chemical Probes Portal: an expert review-based public resource to empower chemical probe assessment, selection and use.. Nucleic Acids Res 2023 Jan 6;51(D1):D1492-D1502.
    doi: 10.1093/nar/gkac909pmc: PMC9825478pubmed: 36268860google scholar: lookup
  31. Kehn-Hall K, Bradfute SB. Understanding host responses to equine encephalitis virus infection: implications for therapeutic development.. Expert Rev Anti Infect Ther 2022 Dec;20(12):1551-1566.
    doi: 10.1080/14787210.2022.2141224pubmed: 36305549google scholar: lookup
  32. Bassetto M., Brancale A.. Chapter Four—The search for antivirals to treat alphavirus infections. Annu. Rep. Med. Chem. 2021;57:133–151.
  33. Nagata L.P., Wong J.P., Hu W.-g., Wu J.Q.. Vaccines and therapeutics for the encephalitic alphaviruses. Future Virol. 2013;8:661–674.
    doi: 10.2217/fvl.13.42google scholar: lookup
  34. Ching KC, F P Ng L, Chai CLL. A compendium of small molecule direct-acting and host-targeting inhibitors as therapies against alphaviruses.. J Antimicrob Chemother 2017 Nov 1;72(11):2973-2989.
    doi: 10.1093/jac/dkx224pmc: PMC7110243pubmed: 28981632google scholar: lookup
  35. Snyder JE, Kulcsar KA, Schultz KL, Riley CP, Neary JT, Marr S, Jose J, Griffin DE, Kuhn RJ. Functional characterization of the alphavirus TF protein.. J Virol 2013 Aug;87(15):8511-23.
    doi: 10.1128/JVI.00449-13pmc: PMC3719798pubmed: 23720714google scholar: lookup
  36. Sharma A, Knollmann-Ritschel B. Current Understanding of the Molecular Basis of Venezuelan Equine Encephalitis Virus Pathogenesis and Vaccine Development.. Viruses 2019 Feb 18;11(2).
    doi: 10.3390/v11020164pmc: PMC6410161pubmed: 30781656google scholar: lookup
  37. Ramsey J, Mukhopadhyay S. Disentangling the Frames, the State of Research on the Alphavirus 6K and TF Proteins.. Viruses 2017 Aug 18;9(8).
    doi: 10.3390/v9080228pmc: PMC5580485pubmed: 28820485google scholar: lookup
  38. Hardy WR, Strauss JH. Processing the nonstructural polyproteins of sindbis virus: nonstructural proteinase is in the C-terminal half of nsP2 and functions both in cis and in trans.. J Virol 1989 Nov;63(11):4653-64.
    doi: 10.1128/jvi.63.11.4653-4664.1989pmc: PMC251099pubmed: 2529379google scholar: lookup
  39. Leung JY, Ng MM, Chu JJ. Replication of alphaviruses: a review on the entry process of alphaviruses into cells.. Adv Virol 2011;2011:249640.
    doi: 10.1155/2011/249640pmc: PMC3265296pubmed: 22312336google scholar: lookup
  40. Jose J, Snyder JE, Kuhn RJ. A structural and functional perspective of alphavirus replication and assembly.. Future Microbiol 2009 Sep;4(7):837-56.
    doi: 10.2217/fmb.09.59pmc: PMC2762864pubmed: 19722838google scholar: lookup
  41. Mukhopadhyay S, Zhang W, Gabler S, Chipman PR, Strauss EG, Strauss JH, Baker TS, Kuhn RJ, Rossmann MG. Mapping the structure and function of the E1 and E2 glycoproteins in alphaviruses.. Structure 2006 Jan;14(1):63-73.
    doi: 10.1016/j.str.2005.07.025pmc: PMC2757649pubmed: 16407066google scholar: lookup
  42. Kim AS, Diamond MS. A molecular understanding of alphavirus entry and antibody protection.. Nat Rev Microbiol 2023 Jun;21(6):396-407.
    doi: 10.1038/s41579-022-00825-7pmc: PMC9734810pubmed: 36474012google scholar: lookup
  43. Gardner CL, Ebel GD, Ryman KD, Klimstra WB. Heparan sulfate binding by natural eastern equine encephalitis viruses promotes neurovirulence.. Proc Natl Acad Sci U S A 2011 Sep 20;108(38):16026-31.
    doi: 10.1073/pnas.1110617108pmc: PMC3179095pubmed: 21896745google scholar: lookup
  44. Mudhakir D, Harashima H. Learning from the viral journey: how to enter cells and how to overcome intracellular barriers to reach the nucleus.. AAPS J 2009 Mar;11(1):65-77.
    doi: 10.1208/s12248-009-9080-9pmc: PMC2664881pubmed: 19194803google scholar: lookup
  45. Carvalho CAM, Silva JL, Oliveira AC, Gomes AMO. On the entry of an emerging arbovirus into host cells: Mayaro virus takes the highway to the cytoplasm through fusion with early endosomes and caveolae-derived vesicles.. PeerJ 2017;5:e3245.
    doi: 10.7717/peerj.3245pmc: PMC5410162pubmed: 28462045google scholar: lookup
  46. Lee CHR, Mohamed Hussain K, Chu JJH. Macropinocytosis dependent entry of Chikungunya virus into human muscle cells.. PLoS Negl Trop Dis 2019 Aug;13(8):e0007610.
    doi: 10.1371/journal.pntd.0007610pmc: PMC6730948pubmed: 31449523google scholar: lookup
  47. Paredes AM, Ferreira D, Horton M, Saad A, Tsuruta H, Johnston R, Klimstra W, Ryman K, Hernandez R, Chiu W, Brown DT. Conformational changes in Sindbis virions resulting from exposure to low pH and interactions with cells suggest that cell penetration may occur at the cell surface in the absence of membrane fusion.. Virology 2004 Jul 1;324(2):373-86.
    doi: 10.1016/j.virol.2004.03.046pubmed: 15207623google scholar: lookup
  48. Vancini R, Wang G, Ferreira D, Hernandez R, Brown DT. Alphavirus genome delivery occurs directly at the plasma membrane in a time- and temperature-dependent process.. J Virol 2013 Apr;87(8):4352-9.
    doi: 10.1128/JVI.03412-12pmc: PMC3624389pubmed: 23388718google scholar: lookup
  49. Cain MD, Salimi H, Gong Y, Yang L, Hamilton SL, Heffernan JR, Hou J, Miller MJ, Klein RS. Virus entry and replication in the brain precedes blood-brain barrier disruption during intranasal alphavirus infection.. J Neuroimmunol 2017 Jul 15;308:118-130.
    doi: 10.1016/j.jneuroim.2017.04.008pmc: PMC5694394pubmed: 28501330google scholar: lookup
  50. Sharma A, Bhomia M, Honnold SP, Maheshwari RK. Role of adhesion molecules and inflammation in Venezuelan equine encephalitis virus infected mouse brain.. Virol J 2011 Apr 29;8:197.
    doi: 10.1186/1743-422X-8-197pmc: PMC3113303pubmed: 21529366google scholar: lookup
  51. Jackson AC, Rossiter JP. Apoptotic cell death is an important cause of neuronal injury in experimental Venezuelan equine encephalitis virus infection of mice.. Acta Neuropathol 1997 Apr;93(4):349-53.
    doi: 10.1007/s004010050626pubmed: 9113200google scholar: lookup
  52. Schoneboom BA, Catlin KM, Marty AM, Grieder FB. Inflammation is a component of neurodegeneration in response to Venezuelan equine encephalitis virus infection in mice.. J Neuroimmunol 2000 Sep 22;109(2):132-46.
    doi: 10.1016/S0165-5728(00)00290-3pubmed: 10996215google scholar: lookup
  53. Risner K, Ahmed A, Bakovic A, Kortchak S, Bhalla N, Narayanan A. Efficacy of FDA-Approved Anti-Inflammatory Drugs Against Venezuelan Equine Encephalitis Virus Infection.. Viruses 2019 Dec 12;11(12).
    doi: 10.3390/v11121151pmc: PMC6950191pubmed: 31842327google scholar: lookup
  54. MacMicking JD. Interferon-inducible effector mechanisms in cell-autonomous immunity.. Nat Rev Immunol 2012 Apr 25;12(5):367-82.
    doi: 10.1038/nri3210pmc: PMC4150610pubmed: 22531325google scholar: lookup
  55. Crosse KM, Monson EA, Beard MR, Helbig KJ. Interferon-Stimulated Genes as Enhancers of Antiviral Innate Immune Signaling.. J Innate Immun 2018;10(2):85-93.
    doi: 10.1159/000484258pmc: PMC5969054pubmed: 29186718google scholar: lookup
  56. Zhang Y, Burke CW, Ryman KD, Klimstra WB. Identification and characterization of interferon-induced proteins that inhibit alphavirus replication.. J Virol 2007 Oct;81(20):11246-55.
    doi: 10.1128/JVI.01282-07pmc: PMC2045553pubmed: 17686841google scholar: lookup
  57. Gall B, Pryke K, Abraham J, Mizuno N, Botto S, Sali TM, Broeckel R, Haese N, Nilsen A, Placzek A, Morrison T, Heise M, Streblow D, DeFilippis V. Emerging Alphaviruses Are Sensitive to Cellular States Induced by a Novel Small-Molecule Agonist of the STING Pathway.. J Virol 2018 Mar 15;92(6).
    doi: 10.1128/JVI.01913-17pmc: PMC5827377pubmed: 29263267google scholar: lookup
  58. Cavlar T, Deimling T, Ablasser A, Hopfner KP, Hornung V. Species-specific detection of the antiviral small-molecule compound CMA by STING.. EMBO J 2013 May 15;32(10):1440-50.
    doi: 10.1038/emboj.2013.86pmc: PMC3655471pubmed: 23604073google scholar: lookup
  59. Liu Y, Lu X, Qin N, Qiao Y, Xing S, Liu W, Feng F, Liu Z, Sun H. STING, a promising target for small molecular immune modulator: A review.. Eur J Med Chem 2021 Feb 5;211:113113.
    doi: 10.1016/j.ejmech.2020.113113pubmed: 33360799google scholar: lookup
  60. Ekins S, Lane TR, Madrid PB. Tilorone: a Broad-Spectrum Antiviral Invented in the USA and Commercialized in Russia and beyond.. Pharm Res 2020 Mar 25;37(4):71.
    doi: 10.1007/s11095-020-02799-8pmc: PMC7100484pubmed: 32215760google scholar: lookup
  61. Ekins S, Lingerfelt MA, Comer JE, Freiberg AN, Mirsalis JC, O'Loughlin K, Harutyunyan A, McFarlane C, Green CE, Madrid PB. Efficacy of Tilorone Dihydrochloride against Ebola Virus Infection.. Antimicrob Agents Chemother 2018 Feb;62(2).
    doi: 10.1128/AAC.01711-17pmc: PMC5786809pubmed: 29133569google scholar: lookup
  62. Ekins S, Madrid PB. Tilorone, a Broad-Spectrum Antiviral for Emerging Viruses.. Antimicrob Agents Chemother 2020 Apr 21;64(5).
    doi: 10.1128/AAC.00440-20pmc: PMC7179581pubmed: 32205350google scholar: lookup
  63. Keyer V, Syzdykova L, Zauatbayeva G, Zhulikeyeva A, Ramanculov Y, Shustov AV, Shulgau Z. Tilorone and Cridanimod Protect Mice and Show Antiviral Activity in Rats despite Absence of the Interferon-Inducing Effect in Rats.. Pharmaceuticals (Basel) 2022 May 17;15(5).
    doi: 10.3390/ph15050617pmc: PMC9143969pubmed: 35631443google scholar: lookup
  64. Alam S, Javor S, Degardin M, Ajami D, Rebek M, Kissner TL, Waag DM, Rebek J Jr, Saikh KU. Structure-Based Design and Synthesis of a Small Molecule that Exhibits Anti-inflammatory Activity by Inhibition of MyD88-mediated Signaling to Bacterial Toxin Exposure.. Chem Biol Drug Des 2015 Aug;86(2):200-9.
    doi: 10.1111/cbdd.12477pubmed: 25393063google scholar: lookup
  65. Sharma A, Maheshwari RK. Oligonucleotide array analysis of Toll-like receptors and associated signalling genes in Venezuelan equine encephalitis virus-infected mouse brain.. J Gen Virol 2009 Aug;90(Pt 8):1836-1847.
    doi: 10.1099/vir.0.010280-0pubmed: 19369408google scholar: lookup
  66. Fuse K, Chan G, Liu Y, Gudgeon P, Husain M, Chen M, Yeh WC, Akira S, Liu PP. Myeloid differentiation factor-88 plays a crucial role in the pathogenesis of Coxsackievirus B3-induced myocarditis and influences type I interferon production.. Circulation 2005 Oct 11;112(15):2276-85.
    doi: 10.1161/CIRCULATIONAHA.105.536433pubmed: 16216974google scholar: lookup
  67. Aguilar PV, Adams AP, Wang E, Kang W, Carrara AS, Anishchenko M, Frolov I, Weaver SC. Structural and nonstructural protein genome regions of eastern equine encephalitis virus are determinants of interferon sensitivity and murine virulence.. J Virol 2008 May;82(10):4920-30.
    doi: 10.1128/JVI.02514-07pmc: PMC2346730pubmed: 18353963google scholar: lookup
  68. Saikh KU, Morazzani EM, Piper AE, Bakken RR, Glass PJ. A small molecule inhibitor of MyD88 exhibits broad spectrum antiviral activity by up regulation of type I interferon.. Antiviral Res 2020 Sep;181:104854.
    doi: 10.1016/j.antiviral.2020.104854pubmed: 32621945google scholar: lookup
  69. Fulcher AJ, Jans DA. Regulation of nucleocytoplasmic trafficking of viral proteins: an integral role in pathogenesis?. Biochim Biophys Acta 2011 Dec;1813(12):2176-90.
    doi: 10.1016/j.bbamcr.2011.03.019pmc: PMC7114211pubmed: 21530593google scholar: lookup
  70. Caly L, Wagstaff KM, Jans DA. Nuclear trafficking of proteins from RNA viruses: potential target for antivirals?. Antiviral Res 2012 Sep;95(3):202-6.
    doi: 10.1016/j.antiviral.2012.06.008pubmed: 22750233google scholar: lookup
  71. Atasheva S, Fish A, Fornerod M, Frolova EI. Venezuelan equine Encephalitis virus capsid protein forms a tetrameric complex with CRM1 and importin alpha/beta that obstructs nuclear pore complex function.. J Virol 2010 May;84(9):4158-71.
    doi: 10.1128/JVI.02554-09pmc: PMC2863722pubmed: 20147401google scholar: lookup
  72. Ryman KD, Klimstra WB. Host responses to alphavirus infection.. Immunol Rev 2008 Oct;225:27-45.
    doi: 10.1111/j.1600-065X.2008.00670.xpubmed: 18837774google scholar: lookup
  73. Shechter S, Thomas DR, Lundberg L, Pinkham C, Lin SC, Wagstaff KM, Debono A, Kehn-Hall K, Jans DA. Novel inhibitors targeting Venezuelan equine encephalitis virus capsid protein identified using In Silico Structure-Based-Drug-Design.. Sci Rep 2017 Dec 18;7(1):17705.
    doi: 10.1038/s41598-017-17672-9pmc: PMC5735092pubmed: 29255256google scholar: lookup
  74. Wagstaff KM, Rawlinson SM, Hearps AC, Jans DA. An AlphaScreen®-based assay for high-throughput screening for specific inhibitors of nuclear import.. J Biomol Screen 2011 Feb;16(2):192-200.
    doi: 10.1177/1087057110390360pubmed: 21297106google scholar: lookup
  75. Wagstaff KM, Sivakumaran H, Heaton SM, Harrich D, Jans DA. Ivermectin is a specific inhibitor of importin α/β-mediated nuclear import able to inhibit replication of HIV-1 and dengue virus.. Biochem J 2012 May 1;443(3):851-6.
    doi: 10.1042/BJ20120150pmc: PMC3327999pubmed: 22417684google scholar: lookup
  76. Thomas DR, Lundberg L, Pinkham C, Shechter S, DeBono A, Baell J, Wagstaff KM, Hick CA, Kehn-Hall K, Jans DA. Identification of novel antivirals inhibiting recognition of Venezuelan equine encephalitis virus capsid protein by the Importin α/β1 heterodimer through high-throughput screening.. Antiviral Res 2018 Mar;151:8-19.
    doi: 10.1016/j.antiviral.2018.01.007pubmed: 29337164google scholar: lookup
  77. Lundberg L, Fontenot J, Lin SC, Pinkham C, Carey BD, Campbell CE, Kehn-Hall K. Venezuelan Equine Encephalitis Virus Capsid Implicated in Infection-Induced Cell Cycle Delay in vitro.. Front Microbiol 2018;9:3126.
    doi: 10.3389/fmicb.2018.03126pmc: PMC6315117pubmed: 30631316google scholar: lookup
  78. Henderson JT, Hwang AC, Harper CC, Stewart FH. Safety of mifepristone abortions in clinical use.. Contraception 2005 Sep;72(3):175-8.
    doi: 10.1016/j.contraception.2005.03.011pubmed: 16102550google scholar: lookup
  79. Schaff EA. Mifepristone: ten years later.. Contraception 2010 Jan;81(1):1-7.
    doi: 10.1016/j.contraception.2009.08.004pubmed: 20004266google scholar: lookup
  80. Lundberg L, Pinkham C, Baer A, Amaya M, Narayanan A, Wagstaff KM, Jans DA, Kehn-Hall K. Nuclear import and export inhibitors alter capsid protein distribution in mammalian cells and reduce Venezuelan Equine Encephalitis Virus replication.. Antiviral Res 2013 Dec;100(3):662-72.
    doi: 10.1016/j.antiviral.2013.10.004pubmed: 24161512google scholar: lookup
  81. DeBono A, Thomas DR, Lundberg L, Pinkham C, Cao Y, Graham JD, Clarke CL, Wagstaff KM, Shechter S, Kehn-Hall K, Jans DA. Novel RU486 (mifepristone) analogues with increased activity against Venezuelan Equine Encephalitis Virus but reduced progesterone receptor antagonistic activity.. Sci Rep 2019 Feb 22;9(1):2634.
    doi: 10.1038/s41598-019-38671-ypmc: PMC6385310pubmed: 30796232google scholar: lookup
  82. Schor S, Einav S. Repurposing of Kinase Inhibitors as Broad-Spectrum Antiviral Drugs.. DNA Cell Biol 2018 Feb;37(2):63-69.
    doi: 10.1089/dna.2017.4033pmc: PMC5804095pubmed: 29148875google scholar: lookup
  83. Pillaiyar T, Laufer S. Kinases as Potential Therapeutic Targets for Anti-coronaviral Therapy.. J Med Chem 2022 Jan 27;65(2):955-982.
    doi: 10.1021/acs.jmedchem.1c00335pubmed: 34081439google scholar: lookup
  84. García-Cárceles J, Caballero E, Gil C, Martínez A. Kinase Inhibitors as Underexplored Antiviral Agents.. J Med Chem 2022 Jan 27;65(2):935-954.
    doi: 10.1021/acs.jmedchem.1c00302pmc: PMC8802305pubmed: 33970631google scholar: lookup
  85. Yi F, Guo J, Dabbagh D, Spear M, He S, Kehn-Hall K, Fontenot J, Yin Y, Bibian M, Park CM, Zheng K, Park HJ, Soloveva V, Gharaibeh D, Retterer C, Zamani R, Pitt ML, Naughton J, Jiang Y, Shang H, Hakami RM, Ling B, Young JAT, Bavari S, Xu X, Feng Y, Wu Y. Discovery of Novel Small-Molecule Inhibitors of LIM Domain Kinase for Inhibiting HIV-1.. J Virol 2017 Jul 1;91(13).
    doi: 10.1128/JVI.02418-16pmc: PMC5469273pubmed: 28381571google scholar: lookup
  86. Spear M, Wu Y. Viral exploitation of actin: force-generation and scaffolding functions in viral infection.. Virol Sin 2014 Jun;29(3):139-47.
    doi: 10.1007/s12250-014-3476-0pmc: PMC4373664pubmed: 24938714google scholar: lookup
  87. Vorster PJ, Guo J, Yoder A, Wang W, Zheng Y, Xu X, Yu D, Spear M, Wu Y. LIM kinase 1 modulates cortical actin and CXCR4 cycling and is activated by HIV-1 to initiate viral infection.. J Biol Chem 2011 Apr 8;286(14):12554-64.
    doi: 10.1074/jbc.M110.182238pmc: PMC3069457pubmed: 21321123google scholar: lookup
  88. Wen X, Ding L, Wang JJ, Qi M, Hammonds J, Chu H, Chen X, Hunter E, Spearman P. ROCK1 and LIM kinase modulate retrovirus particle release and cell-cell transmission events.. J Virol 2014 Jun;88(12):6906-21.
    doi: 10.1128/JVI.00023-14pmc: PMC4054354pubmed: 24696479google scholar: lookup
  89. Wilhelm S, Carter C, Lynch M, Lowinger T, Dumas J, Smith RA, Schwartz B, Simantov R, Kelley S. Discovery and development of sorafenib: a multikinase inhibitor for treating cancer.. Nat Rev Drug Discov 2006 Oct;5(10):835-44.
    doi: 10.1038/nrd2130pubmed: 17016424google scholar: lookup
  90. Ibrahim N, Yu Y, Walsh WR, Yang JL. Molecular targeted therapies for cancer: sorafenib mono-therapy and its combination with other therapies (review).. Oncol Rep 2012 May;27(5):1303-11.
    doi: 10.3892/or.2012.1675pubmed: 22323095google scholar: lookup
  91. Wilhelm SM, Adnane L, Newell P, Villanueva A, Llovet JM, Lynch M. Preclinical overview of sorafenib, a multikinase inhibitor that targets both Raf and VEGF and PDGF receptor tyrosine kinase signaling.. Mol Cancer Ther 2008 Oct;7(10):3129-40.
    doi: 10.1158/1535-7163.MCT-08-0013pubmed: 18852116google scholar: lookup
  92. Lundberg L, Brahms A, Hooper I, Carey B, Lin SC, Dahal B, Narayanan A, Kehn-Hall K. Repurposed FDA-Approved drug sorafenib reduces replication of Venezuelan equine encephalitis virus and other alphaviruses.. Antiviral Res 2018 Sep;157:57-67.
    doi: 10.1016/j.antiviral.2018.07.005pubmed: 29981794google scholar: lookup
  93. Chen KF, Tai WT, Huang JW, Hsu CY, Chen WL, Cheng AL, Chen PJ, Shiau CW. Sorafenib derivatives induce apoptosis through inhibition of STAT3 independent of Raf.. Eur J Med Chem 2011 Jul;46(7):2845-51.
    doi: 10.1016/j.ejmech.2011.04.007pubmed: 21531053google scholar: lookup
  94. Su TH, Shiau CW, Jao P, Liu CH, Liu CJ, Tai WT, Jeng YM, Yang HC, Tseng TC, Huang HP, Cheng HR, Chen PJ, Chen KF, Kao JH, Chen DS. Sorafenib and its derivative SC-1 exhibit antifibrotic effects through signal transducer and activator of transcription 3 inhibition.. Proc Natl Acad Sci U S A 2015 Jun 9;112(23):7243-8.
    doi: 10.1073/pnas.1507499112pmc: PMC4466718pubmed: 26039995google scholar: lookup
  95. Benedict A, Bansal N, Senina S, Hooper I, Lundberg L, de la Fuente C, Narayanan A, Gutting B, Kehn-Hall K. Repurposing FDA-approved drugs as therapeutics to treat Rift Valley fever virus infection.. Front Microbiol 2015;6:676.
    doi: 10.3389/fmicb.2015.00676pmc: PMC4495339pubmed: 26217313google scholar: lookup
  96. Brahms A, Mudhasani R, Pinkham C, Kota K, Nasar F, Zamani R, Bavari S, Kehn-Hall K. Sorafenib Impedes Rift Valley Fever Virus Egress by Inhibiting Valosin-Containing Protein Function in the Cellular Secretory Pathway.. J Virol 2017 Nov 1;91(21).
    doi: 10.1128/JVI.00968-17pmc: PMC5640838pubmed: 28794043google scholar: lookup
  97. Himmelsbach K, Sauter D, Baumert TF, Ludwig L, Blum HE, Hildt E. New aspects of an anti-tumour drug: sorafenib efficiently inhibits HCV replication.. Gut 2009 Dec;58(12):1644-53.
    doi: 10.1136/gut.2009.182212pubmed: 19710032google scholar: lookup
  98. Lehman CW, Kehn-Hall K, Aggarwal M, Bracci NR, Pan HC, Panny L, Lamb RA, Lin SC. Resveratrol Inhibits Venezuelan Equine Encephalitis Virus Infection by Interfering with the AKT/GSK Pathway.. Plants (Basel) 2021 Feb 12;10(2).
    doi: 10.3390/plants10020346pmc: PMC7918260pubmed: 33673026google scholar: lookup
  99. Thaa B, Biasiotto R, Eng K, Neuvonen M, Götte B, Rheinemann L, Mutso M, Utt A, Varghese F, Balistreri G, Merits A, Ahola T, McInerney GM. Differential Phosphatidylinositol-3-Kinase-Akt-mTOR Activation by Semliki Forest and Chikungunya Viruses Is Dependent on nsP3 and Connected to Replication Complex Internalization.. J Virol 2015 Nov;89(22):11420-37.
    doi: 10.1128/JVI.01579-15pmc: PMC4645633pubmed: 26339054google scholar: lookup
  100. Mazzon M, Castro C, Thaa B, Liu L, Mutso M, Liu X, Mahalingam S, Griffin JL, Marsh M, McInerney GM. Alphavirus-induced hyperactivation of PI3K/AKT directs pro-viral metabolic changes.. PLoS Pathog 2018 Jan;14(1):e1006835.
    doi: 10.1371/journal.ppat.1006835pmc: PMC5805360pubmed: 29377936google scholar: lookup
  101. Saqib U, Kelley TT, Panguluri SK, Liu D, Savai R, Baig MS, Schürer SC. Polypharmacology or Promiscuity? Structural Interactions of Resveratrol With Its Bandwagon of Targets.. Front Pharmacol 2018;9:1201.
    doi: 10.3389/fphar.2018.01201pmc: PMC6207623pubmed: 30405416google scholar: lookup
  102. Amaya M, Voss K, Sampey G, Senina S, de la Fuente C, Mueller C, Calvert V, Kehn-Hall K, Carpenter C, Kashanchi F, Bailey C, Mogelsvang S, Petricoin E, Narayanan A. The role of IKKβ in Venezuelan equine encephalitis virus infection.. PLoS One 2014;9(2):e86745.
    doi: 10.1371/journal.pone.0086745pmc: PMC3929299pubmed: 24586253google scholar: lookup
  103. Le Negrate G. Viral interference with innate immunity by preventing NF-κB activity.. Cell Microbiol 2012 Feb;14(2):168-81.
    doi: 10.1111/j.1462-5822.2011.01720.xpubmed: 22050732google scholar: lookup
  104. Karin M. The beginning of the end: IkappaB kinase (IKK) and NF-kappaB activation.. J Biol Chem 1999 Sep 24;274(39):27339-42.
    doi: 10.1074/jbc.274.39.27339pubmed: 10488062google scholar: lookup
  105. Hayden MS, Ghosh S. Signaling to NF-kappaB.. Genes Dev 2004 Sep 15;18(18):2195-224.
    doi: 10.1101/gad.1228704pubmed: 15371334google scholar: lookup
  106. Santoro MG, Rossi A, Amici C. NF-kappaB and virus infection: who controls whom.. EMBO J 2003 Jun 2;22(11):2552-60.
    doi: 10.1093/emboj/cdg267pmc: PMC156764pubmed: 12773372google scholar: lookup
  107. Bakovic A, Bhalla N, Kortchak S, Sun C, Zhou W, Ahmed A, Risner K, Klimstra WB, Narayanan A. Venezuelan Equine Encephalitis Virus nsP3 Phosphorylation Can Be Mediated by IKKβ Kinase Activity and Abrogation of Phosphorylation Inhibits Negative-Strand Synthesis.. Viruses 2020 Sep 13;12(9).
    doi: 10.3390/v12091021pmc: PMC7551587pubmed: 32933112google scholar: lookup
  108. Ammosova T, Platonov M, Ivanov A, Kont YS, Kumari N, Kehn-Hall K, Jerebtsova M, Kulkarni AA, Uren A, Kovalskyy D, Nekhai S. 1E7-03, a low MW compound targeting host protein phosphatase-1, inhibits HIV-1 transcription.. Br J Pharmacol 2014 Nov;171(22):5059-75.
    doi: 10.1111/bph.12863pmc: PMC4253456pubmed: 25073485google scholar: lookup
  109. Lin X, Kumari N, DeMarino C, Kont YS, Ammosova T, Kulkarni A, Jerebtsova M, Vazquez-Meves G, Ivanov A, Dmytro K, Üren A, Kashanchi F, Nekhai S. Inhibition of HIV-1 infection in humanized mice and metabolic stability of protein phosphatase-1-targeting small molecule 1E7-03.. Oncotarget 2017 Sep 29;8(44):76749-76769.
    doi: 10.18632/oncotarget.19999pmc: PMC5652740pubmed: 29100346google scholar: lookup
  110. Carey BD, Ammosova T, Pinkham C, Lin X, Zhou W, Liotta LA, Nekhai S, Kehn-Hall K. Protein Phosphatase 1α Interacts with Venezuelan Equine Encephalitis Virus Capsid Protein and Regulates Viral Replication through Modulation of Capsid Phosphorylation.. J Virol 2018 Aug 1;92(15).
    doi: 10.1128/JVI.02068-17pmc: PMC6052284pubmed: 29769351google scholar: lookup
  111. Ellgaard L, Helenius A. Quality control in the endoplasmic reticulum.. Nat Rev Mol Cell Biol 2003 Mar;4(3):181-91.
    doi: 10.1038/nrm1052pubmed: 12612637google scholar: lookup
  112. Singh I, Doms RW, Wagner KR, Helenius A. Intracellular transport of soluble and membrane-bound glycoproteins: folding, assembly and secretion of anchor-free influenza hemagglutinin.. EMBO J 1990 Mar;9(3):631-9.
    doi: 10.1002/j.1460-2075.1990.tb08155.xpmc: PMC551716pubmed: 2178922google scholar: lookup
  113. Mulvey M, Brown DT. Involvement of the molecular chaperone BiP in maturation of Sindbis virus envelope glycoproteins.. J Virol 1995 Mar;69(3):1621-7.
    doi: 10.1128/jvi.69.3.1621-1627.1995pmc: PMC188759pubmed: 7853497google scholar: lookup
  114. Choukhi A, Ung S, Wychowski C, Dubuisson J. Involvement of endoplasmic reticulum chaperones in the folding of hepatitis C virus glycoproteins.. J Virol 1998 May;72(5):3851-8.
    doi: 10.1128/JVI.72.5.3851-3858.1998pmc: PMC109609pubmed: 9557669google scholar: lookup
  115. Little E, Ramakrishnan M, Roy B, Gazit G, Lee AS. The glucose-regulated proteins (GRP78 and GRP94): functions, gene regulation, and applications.. Crit Rev Eukaryot Gene Expr 1994;4(1):1-18.
    doi: 10.1615/CritRevEukarGeneExpr.v4.i1.10pubmed: 7987045google scholar: lookup
  116. Pfaffenbach KT, Lee AS. The critical role of GRP78 in physiologic and pathologic stress.. Curr Opin Cell Biol 2011 Apr;23(2):150-6.
    doi: 10.1016/j.ceb.2010.09.007pmc: PMC3043145pubmed: 20970977google scholar: lookup
  117. Barrera MD, Callahan V, Akhrymuk I, Bhalla N, Zhou W, Campbell C, Narayanan A, Kehn-Hall K. Proteomic Discovery of VEEV E2-Host Partner Interactions Identifies GRP78 Inhibitor HA15 as a Potential Therapeutic for Alphavirus Infections.. Pathogens 2021 Mar 2;10(3).
    doi: 10.3390/pathogens10030283pmc: PMC8000471pubmed: 33801554google scholar: lookup
  118. Seipke RF, Barke J, Brearley C, Hill L, Yu DW, Goss RJ, Hutchings MI. A single Streptomyces symbiont makes multiple antifungals to support the fungus farming ant Acromyrmex octospinosus.. PLoS One 2011;6(8):e22028.
    doi: 10.1371/journal.pone.0022028pmc: PMC3153929pubmed: 21857911google scholar: lookup
  119. Shum D, Smith JL, Hirsch AJ, Bhinder B, Radu C, Stein DA, Nelson JA, Früh K, Djaballah H. High-content assay to identify inhibitors of dengue virus infection.. Assay Drug Dev Technol 2010 Oct;8(5):553-70.
    doi: 10.1089/adt.2010.0321pmc: PMC2962577pubmed: 20973722google scholar: lookup
  120. Hui EK, Nayak DP. Role of ATP in influenza virus budding.. Virology 2001 Nov 25;290(2):329-41.
    doi: 10.1006/viro.2001.1181pubmed: 11883197google scholar: lookup
  121. Raveh A, Delekta PC, Dobry CJ, Peng W, Schultz PJ, Blakely PK, Tai AW, Matainaho T, Irani DN, Sherman DH, Miller DJ. Discovery of potent broad spectrum antivirals derived from marine actinobacteria.. PLoS One 2013;8(12):e82318.
    doi: 10.1371/journal.pone.0082318pmc: PMC3857800pubmed: 24349254google scholar: lookup
  122. Hamilton PB, Carroll FI, Rutledge JH, Mason JE, Harris BS, Fenske CS, Wall ME. Simple isolation of antimycin A1 and some of its toxicological properties.. Appl Microbiol 1969 Jan;17(1):102-5.
    doi: 10.1128/am.17.1.102-105.1969pmc: PMC377621pubmed: 5774751google scholar: lookup
  123. Kasprzyk R, Jemielity J. Enzymatic Assays to Explore Viral mRNA Capping Machinery.. Chembiochem 2021 Dec 2;22(23):3236-3253.
    doi: 10.1002/cbic.202100291pmc: PMC8426721pubmed: 34291555google scholar: lookup
  124. Ferreira-Ramos AS, Li C, Eydoux C, Contreras JM, Morice C, Quérat G, Gigante A, Pérez Pérez MJ, Jung ML, Canard B, Guillemot JC, Decroly E, Coutard B. Approved drugs screening against the nsP1 capping enzyme of Venezuelan equine encephalitis virus using an immuno-based assay.. Antiviral Res 2019 Mar;163:59-69.
    doi: 10.1016/j.antiviral.2019.01.003pubmed: 30639438google scholar: lookup
  125. Li C, Guillén J, Rabah N, Blanjoie A, Debart F, Vasseur JJ, Canard B, Decroly E, Coutard B. mRNA Capping by Venezuelan Equine Encephalitis Virus nsP1: Functional Characterization and Implications for Antiviral Research.. J Virol 2015 Aug;89(16):8292-303.
    doi: 10.1128/JVI.00599-15pmc: PMC4524220pubmed: 26041283google scholar: lookup
  126. Decroly E, Ferron F, Lescar J, Canard B. Conventional and unconventional mechanisms for capping viral mRNA.. Nat Rev Microbiol 2011 Dec 5;10(1):51-65.
    doi: 10.1038/nrmicro2675pmc: PMC7097100pubmed: 22138959google scholar: lookup
  127. Ferron F, Decroly E, Selisko B, Canard B. The viral RNA capping machinery as a target for antiviral drugs.. Antiviral Res 2012 Oct;96(1):21-31.
    doi: 10.1016/j.antiviral.2012.07.007pmc: PMC7114304pubmed: 22841701google scholar: lookup
  128. Rabah N, Ortega Granda O, Quérat G, Canard B, Decroly E, Coutard B. Mutations on VEEV nsP1 relate RNA capping efficiency to ribavirin susceptibility.. Antiviral Res 2020 Oct;182:104883.
    doi: 10.1016/j.antiviral.2020.104883pubmed: 32750467google scholar: lookup
  129. Delang L, Li C, Tas A, Quérat G, Albulescu IC, De Burghgraeve T, Guerrero NA, Gigante A, Piorkowski G, Decroly E, Jochmans D, Canard B, Snijder EJ, Pérez-Pérez MJ, van Hemert MJ, Coutard B, Leyssen P, Neyts J. The viral capping enzyme nsP1: a novel target for the inhibition of chikungunya virus infection.. Sci Rep 2016 Aug 22;6:31819.
    doi: 10.1038/srep31819pmc: PMC4992889pubmed: 27545976google scholar: lookup
  130. Rupp JC, Sokoloski KJ, Gebhart NN, Hardy RW. Alphavirus RNA synthesis and non-structural protein functions.. J Gen Virol 2015 Sep;96(9):2483-2500.
    doi: 10.1099/jgv.0.000249pmc: PMC4635493pubmed: 26219641google scholar: lookup
  131. Abu Bakar F, Ng LFP. Nonstructural Proteins of Alphavirus-Potential Targets for Drug Development.. Viruses 2018 Feb 9;10(2).
    doi: 10.3390/v10020071pmc: PMC5850378pubmed: 29425115google scholar: lookup
  132. Bozóki B, Mótyán JA, Hoffka G, Waugh DS, Tőzsér J. Specificity Studies of the Venezuelan Equine Encephalitis Virus Non-Structural Protein 2 Protease Using Recombinant Fluorescent Substrates.. Int J Mol Sci 2020 Oct 16;21(20).
    doi: 10.3390/ijms21207686pmc: PMC7593941pubmed: 33081394google scholar: lookup
  133. Morazzani EM, Compton JR, Leary DH, Berry AV, Hu X, Marugan JJ, Glass PJ, Legler PM. Proteolytic cleavage of host proteins by the Group IV viral proteases of Venezuelan equine encephalitis virus and Zika virus.. Antiviral Res 2019 Apr;164:106-122.
    doi: 10.1016/j.antiviral.2019.02.001pmc: PMC9575189pubmed: 30742841google scholar: lookup
  134. Rikkonen M, Peränen J, Kääriäinen L. ATPase and GTPase activities associated with Semliki Forest virus nonstructural protein nsP2.. J Virol 1994 Sep;68(9):5804-10.
    doi: 10.1128/jvi.68.9.5804-5810.1994pmc: PMC236984pubmed: 8057461google scholar: lookup
  135. Gomez de Cedrón M, Ehsani N, Mikkola ML, García JA, Kääriäinen L. RNA helicase activity of Semliki Forest virus replicase protein NSP2.. FEBS Lett 1999 Apr 1;448(1):19-22.
    doi: 10.1016/S0014-5793(99)00321-Xpubmed: 10217401google scholar: lookup
  136. Vasiljeva L, Valmu L, Kääriäinen L, Merits A. Site-specific protease activity of the carboxyl-terminal domain of Semliki Forest virus replicase protein nsP2.. J Biol Chem 2001 Aug 17;276(33):30786-93.
    doi: 10.1074/jbc.M104786200pubmed: 11410598google scholar: lookup
  137. Vasiljeva L, Merits A, Auvinen P, Kääriäinen L. Identification of a novel function of the alphavirus capping apparatus. RNA 5'-triphosphatase activity of Nsp2.. J Biol Chem 2000 Jun 9;275(23):17281-7.
    doi: 10.1074/jbc.M910340199pubmed: 10748213google scholar: lookup
  138. Russo AT, White MA, Watowich SJ. The crystal structure of the Venezuelan equine encephalitis alphavirus nsP2 protease.. Structure 2006 Sep;14(9):1449-58.
    doi: 10.1016/j.str.2006.07.010pubmed: 16962975google scholar: lookup
  139. Hu X, Compton JR, Leary DH, Olson MA, Lee MS, Cheung J, Ye W, Ferrer M, Southall N, Jadhav A, Morazzani EM, Glass PJ, Marugan J, Legler PM. Kinetic, Mutational, and Structural Studies of the Venezuelan Equine Encephalitis Virus Nonstructural Protein 2 Cysteine Protease.. Biochemistry 2016 May 31;55(21):3007-19.
    doi: 10.1021/acs.biochem.5b00992pmc: PMC5290728pubmed: 27030368google scholar: lookup
  140. Zhang H, Harmon M, Radoshitzky SR, Soloveva V, Kane CD, Duplantier AJ, Ogungbe IV. Vinyl Sulfone-Based Inhibitors of Nonstructural Protein 2 Block the Replication of Venezuelan Equine Encephalitis Virus.. ACS Med Chem Lett 2020 Nov 12;11(11):2139-2145.
    doi: 10.1021/acsmedchemlett.0c00215pmc: PMC7667866pubmed: 33214821google scholar: lookup
  141. Haese NN, May NA, Taft-Benz S, Moukha-Chafiq O, Madadi N, Zhang S, Karyakarte SD, Rodzinak KJ, Nguyen TH, Denton M, Streblow AD, Towers NA, Rasmussen L, Bostwick RJ, Maddry JA, Ananthan S, Augelli-Szafran CE, Suto MJ, Sanders W, Moorman N, DeFilippis V, Heise MT, Pathak AK, Streblow DN, Morrison TE. Identification of Quinolinones as Antivirals against Venezuelan Equine Encephalitis Virus.. Antimicrob Agents Chemother 2021 Aug 17;65(9):e0024421.
    doi: 10.1128/AAC.00244-21pmc: PMC8373297pubmed: 34152810google scholar: lookup
  142. Strauss JH, Strauss EG. The alphaviruses: gene expression, replication, and evolution.. Microbiol Rev 1994 Sep;58(3):491-562.
    doi: 10.1128/mr.58.3.491-562.1994pmc: PMC372977pubmed: 7968923google scholar: lookup
  143. Wang YF, Sawicki SG, Sawicki DL. Alphavirus nsP3 functions to form replication complexes transcribing negative-strand RNA.. J Virol 1994 Oct;68(10):6466-75.
    doi: 10.1128/jvi.68.10.6466-6475.1994pmc: PMC237067pubmed: 8083984google scholar: lookup
  144. Götte B, Liu L, McInerney GM. The Enigmatic Alphavirus Non-Structural Protein 3 (nsP3) Revealing Its Secrets at Last.. Viruses 2018 Feb 28;10(3).
    doi: 10.3390/v10030105pmc: PMC5869498pubmed: 29495654google scholar: lookup
  145. Frolov I, Kim DY, Akhrymuk M, Mobley JA, Frolova EI. Hypervariable Domain of Eastern Equine Encephalitis Virus nsP3 Redundantly Utilizes Multiple Cellular Proteins for Replication Complex Assembly.. J Virol 2017 Jul 15;91(14).
    doi: 10.1128/JVI.00371-17pmc: PMC5487569pubmed: 28468889google scholar: lookup
  146. Kim DY, Reynaud JM, Rasalouskaya A, Akhrymuk I, Mobley JA, Frolov I, Frolova EI. New World and Old World Alphaviruses Have Evolved to Exploit Different Components of Stress Granules, FXR and G3BP Proteins, for Assembly of Viral Replication Complexes.. PLoS Pathog 2016 Aug;12(8):e1005810.
    doi: 10.1371/journal.ppat.1005810pmc: PMC4980055pubmed: 27509095google scholar: lookup
  147. Lark T, Keck F, Narayanan A. Interactions of Alphavirus nsP3 Protein with Host Proteins.. Front Microbiol 2017;8:2652.
    doi: 10.3389/fmicb.2017.02652pmc: PMC5767282pubmed: 29375517google scholar: lookup
  148. Foy NJ, Akhrymuk M, Akhrymuk I, Atasheva S, Bopda-Waffo A, Frolov I, Frolova EI. Hypervariable domains of nsP3 proteins of New World and Old World alphaviruses mediate formation of distinct, virus-specific protein complexes.. J Virol 2013 Feb;87(4):1997-2010.
    doi: 10.1128/JVI.02853-12pmc: PMC3571466pubmed: 23221551google scholar: lookup
  149. Nowee G, Bakker JW, Geertsema C, Ros VID, Göertz GP, Fros JJ, Pijlman GP. A Tale of 20 Alphaviruses; Inter-species Diversity and Conserved Interactions Between Viral Non-structural Protein 3 and Stress Granule Proteins.. Front Cell Dev Biol 2021;9:625711.
    doi: 10.3389/fcell.2021.625711pmc: PMC7905232pubmed: 33644063google scholar: lookup
  150. Amaya M, Brooks-Faulconer T, Lark T, Keck F, Bailey C, Raman V, Narayanan A. Venezuelan equine encephalitis virus non-structural protein 3 (nsP3) interacts with RNA helicases DDX1 and DDX3 in infected cells.. Antiviral Res 2016 Jul;131:49-60.
    doi: 10.1016/j.antiviral.2016.04.008pmc: PMC7113772pubmed: 27105836google scholar: lookup
  151. Bakovic A, Bhalla N, Alem F, Campbell C, Zhou W, Narayanan A. Inhibitors of Venezuelan Equine Encephalitis Virus Identified Based on Host Interaction Partners of Viral Non-Structural Protein 3.. Viruses 2021 Aug 3;13(8).
    doi: 10.3390/v13081533pmc: PMC8402862pubmed: 34452398google scholar: lookup
  152. Tomar S, Hardy RW, Smith JL, Kuhn RJ. Catalytic core of alphavirus nonstructural protein nsP4 possesses terminal adenylyltransferase activity.. J Virol 2006 Oct;80(20):9962-9.
    doi: 10.1128/JVI.01067-06pmc: PMC1617302pubmed: 17005674google scholar: lookup
  153. Chen MW, Tan YB, Zheng J, Zhao Y, Lim BT, Cornvik T, Lescar J, Ng LFP, Luo D. Chikungunya virus nsP4 RNA-dependent RNA polymerase core domain displays detergent-sensitive primer extension and terminal adenylyltransferase activities.. Antiviral Res 2017 Jul;143:38-47.
    doi: 10.1016/j.antiviral.2017.04.001pubmed: 28390873google scholar: lookup
  154. Rubach JK, Wasik BR, Rupp JC, Kuhn RJ, Hardy RW, Smith JL. Characterization of purified Sindbis virus nsP4 RNA-dependent RNA polymerase activity in vitro.. Virology 2009 Feb 5;384(1):201-8.
    doi: 10.1016/j.virol.2008.10.030pmc: PMC3107704pubmed: 19036396google scholar: lookup
  155. Ollis DL, Brick P, Hamlin R, Xuong NG, Steitz TA. Structure of large fragment of Escherichia coli DNA polymerase I complexed with dTMP.. Nature 1985 Feb 28-Mar 6;313(6005):762-6.
    doi: 10.1038/313762a0pubmed: 3883192google scholar: lookup
  156. van der Heijden MW, Bol JF. Composition of alphavirus-like replication complexes: involvement of virus and host encoded proteins.. Arch Virol 2002 May;147(5):875-98.
    doi: 10.1007/s00705-001-0773-3pubmed: 12021862google scholar: lookup
  157. Malone B, Campbell EA. Molnupiravir: coding for catastrophe.. Nat Struct Mol Biol 2021 Sep;28(9):706-708.
    doi: 10.1038/s41594-021-00657-8pubmed: 34518697google scholar: lookup
  158. Urakova N, Kuznetsova V, Crossman DK, Sokratian A, Guthrie DB, Kolykhalov AA, Lockwood MA, Natchus MG, Crowley MR, Painter GR, Frolova EI, Frolov I. β-d-N(4)-Hydroxycytidine Is a Potent Anti-alphavirus Compound That Induces a High Level of Mutations in the Viral Genome.. J Virol 2018 Feb 1;92(3).
    doi: 10.1128/JVI.01965-17pmc: PMC5774879pubmed: 29167335google scholar: lookup
  159. Stuyver LJ, Whitaker T, McBrayer TR, Hernandez-Santiago BI, Lostia S, Tharnish PM, Ramesh M, Chu CK, Jordan R, Shi J, Rachakonda S, Watanabe KA, Otto MJ, Schinazi RF. Ribonucleoside analogue that blocks replication of bovine viral diarrhea and hepatitis C viruses in culture.. Antimicrob Agents Chemother 2003 Jan;47(1):244-54.
    doi: 10.1128/AAC.47.1.244-254.2003pmc: PMC149013pubmed: 12499198google scholar: lookup
  160. Costantini VP, Whitaker T, Barclay L, Lee D, McBrayer TR, Schinazi RF, Vinjé J. Antiviral activity of nucleoside analogues against norovirus.. Antivir Ther 2012;17(6):981-91.
    doi: 10.3851/IMP2229pmc: PMC7751060pubmed: 22910194google scholar: lookup
  161. Ehteshami M, Tao S, Zandi K, Hsiao HM, Jiang Y, Hammond E, Amblard F, Russell OO, Merits A, Schinazi RF. Characterization of β-d-N(4)-Hydroxycytidine as a Novel Inhibitor of Chikungunya Virus.. Antimicrob Agents Chemother 2017 Apr;61(4).
    doi: 10.1128/AAC.02395-16pmc: PMC5365705pubmed: 28137799google scholar: lookup
  162. Painter GR, Bowen RA, Bluemling GR, DeBergh J, Edpuganti V, Gruddanti PR, Guthrie DB, Hager M, Kuiper DL, Lockwood MA, Mitchell DG, Natchus MG, Sticher ZM, Kolykhalov AA. The prophylactic and therapeutic activity of a broadly active ribonucleoside analog in a murine model of intranasal venezuelan equine encephalitis virus infection.. Antiviral Res 2019 Nov;171:104597.
    doi: 10.1016/j.antiviral.2019.104597pubmed: 31494195google scholar: lookup
  163. Schroeder CE, Yao T, Sotsky J, Smith RA, Roy S, Chu YK, Guo H, Tower NA, Noah JW, McKellip S, Sosa M, Rasmussen L, Smith LH, White EL, Aubé J, Jonsson CB, Chung D, Golden JE. Development of (E)-2-((1,4-dimethylpiperazin-2-ylidene)amino)-5-nitro-N-phenylbenzamide, ML336: Novel 2-amidinophenylbenzamides as potent inhibitors of venezuelan equine encephalitis virus.. J Med Chem 2014 Oct 23;57(20):8608-21.
    doi: 10.1021/jm501203vpmc: PMC4207539pubmed: 25244572google scholar: lookup
  164. LaBauve AE, Rinker TE, Noureddine A, Serda RE, Howe JY, Sherman MB, Rasley A, Brinker CJ, Sasaki DY, Negrete OA. Lipid-Coated Mesoporous Silica Nanoparticles for the Delivery of the ML336 Antiviral to Inhibit Encephalitic Alphavirus Infection.. Sci Rep 2018 Sep 18;8(1):13990.
    doi: 10.1038/s41598-018-32033-wpmc: PMC6143628pubmed: 30228359google scholar: lookup
  165. Skidmore AM, Adcock RS, Jonsson CB, Golden JE, Chung DH. Benzamidine ML336 inhibits plus and minus strand RNA synthesis of Venezuelan equine encephalitis virus without affecting host RNA production.. Antiviral Res 2020 Feb;174:104674.
    doi: 10.1016/j.antiviral.2019.104674pmc: PMC6935354pubmed: 31816348google scholar: lookup
  166. Jonsson CB, Cao X, Lee J, Gabbard JD, Chu YK, Fitzpatrick EA, Julander J, Chung DH, Stabenow J, Golden JE. Efficacy of a ML336 derivative against Venezuelan and eastern equine encephalitis viruses.. Antiviral Res 2019 Jul;167:25-34.
    doi: 10.1016/j.antiviral.2019.04.004pmc: PMC7305796pubmed: 30970271google scholar: lookup
  167. Lee J, Parvathareddy J, Yang D, Bansal S, O'Connell K, Golden JE, Jonsson CB. Emergence and Magnitude of ML336 Resistance in Venezuelan Equine Encephalitis Virus Depend on the Microenvironment.. J Virol 2020 Oct 27;94(22).
    doi: 10.1128/JVI.00317-20pmc: PMC7592223pubmed: 32878897google scholar: lookup
  168. Nguyen TH, Haese NN, Madadi N, Sarkar S, Bonin K, Streblow CE, Taft-Benz S, Tower NA, Rasmussen L, Bostwick R, Augelli-Szafran CE, Suto MJ, Morrison TE, DeFilippis V, Heise MT, Streblow DN, Pathak AK. Studies on Dibenzylamines as Inhibitors of Venezuelan Equine Encephalitis Virus.. ACS Infect Dis 2019 Dec 13;5(12):2014-2028.
    doi: 10.1021/acsinfecdis.9b00035pubmed: 31257853google scholar: lookup
  169. Ryan MC, Kim E, Cao X, Reichard W, Ogorek TJ, Das P, Jonsson CB, Baudry J, Chung D, Golden JE. Piperazinobenzodiazepinones: New Encephalitic Alphavirus Inhibitors via Ring Expansion of 2-Dichloromethylquinazolinones.. ACS Med Chem Lett 2022 Apr 14;13(4):546-553.
    doi: 10.1021/acsmedchemlett.1c00539pmc: PMC9014857pubmed: 35450382google scholar: lookup
  170. Ahmed SK, Haese NN, Cowan JT, Pathak V, Moukha-Chafiq O, Smith VJ, Rodzinak KJ, Ahmad F, Zhang S, Bonin KM, Streblow AD, Streblow CE, Kreklywich CN, Morrison C, Sarkar S, Moorman N, Sander W, Allen R, DeFilippis V, Tekwani BL, Wu M, Hirsch AJ, Smith JL, Tower NA, Rasmussen L, Bostwick R, Maddry JA, Ananthan S, Gerdes JM, Augelli-Szafran CE, Suto MJ, Morrison TE, Heise MT, Streblow DN, Pathak AK. Targeting Chikungunya Virus Replication by Benzoannulene Inhibitors.. J Med Chem 2021 Apr 22;64(8):4762-4786.
    doi: 10.1021/acs.jmedchem.0c02183pmc: PMC9774970pubmed: 33835811google scholar: lookup
  171. Wang QY, Bushell S, Qing M, Xu HY, Bonavia A, Nunes S, Zhou J, Poh MK, Florez de Sessions P, Niyomrattanakit P, Dong H, Hoffmaster K, Goh A, Nilar S, Schul W, Jones S, Kramer L, Compton T, Shi PY. Inhibition of dengue virus through suppression of host pyrimidine biosynthesis.. J Virol 2011 Jul;85(13):6548-56.
    doi: 10.1128/JVI.02510-10pmc: PMC3126545pubmed: 21507975google scholar: lookup
  172. Luthra P, Naidoo J, Pietzsch CA, De S, Khadka S, Anantpadma M, Williams CG, Edwards MR, Davey RA, Bukreyev A, Ready JM, Basler CF. Inhibiting pyrimidine biosynthesis impairs Ebola virus replication through depletion of nucleoside pools and activation of innate immune responses.. Antiviral Res 2018 Oct;158:288-302.
    doi: 10.1016/j.antiviral.2018.08.012pmc: PMC6436837pubmed: 30144461google scholar: lookup
  173. Li N, Wang Z, Wang R, Zhang ZR, Zhang YN, Deng CL, Zhang B, Shang LQ, Ye HQ. In Vitro Inhibition of Alphaviruses by Lycorine.. Virol Sin 2021 Dec;36(6):1465-1474.
    doi: 10.1007/s12250-021-00438-zpmc: PMC8353614pubmed: 34374926google scholar: lookup
  174. Roy M, Liang L, Xiao X, Feng P, Ye M, Liu J. Lycorine: A prospective natural lead for anticancer drug discovery.. Biomed Pharmacother 2018 Nov;107:615-624.
    doi: 10.1016/j.biopha.2018.07.147pmc: PMC7127747pubmed: 30114645google scholar: lookup
  175. Wang H, Guo T, Yang Y, Yu L, Pan X, Li Y. Lycorine Derivative LY-55 Inhibits EV71 and CVA16 Replication Through Downregulating Autophagy.. Front Cell Infect Microbiol 2019;9:277.
    doi: 10.3389/fcimb.2019.00277pmc: PMC6692562pubmed: 31448243google scholar: lookup
  176. He J, Qi WB, Wang L, Tian J, Jiao PR, Liu GQ, Ye WC, Liao M. Amaryllidaceae alkaloids inhibit nuclear-to-cytoplasmic export of ribonucleoprotein (RNP) complex of highly pathogenic avian influenza virus H5N1.. Influenza Other Respir Viruses 2013 Nov;7(6):922-31.
    doi: 10.1111/irv.12035pmc: PMC4634243pubmed: 23136954google scholar: lookup
  177. Liu J, Yang Y, Xu Y, Ma C, Qin C, Zhang L. Lycorine reduces mortality of human enterovirus 71-infected mice by inhibiting virus replication.. Virol J 2011 Oct 27;8:483.
    doi: 10.1186/1743-422X-8-483pmc: PMC3212826pubmed: 22029605google scholar: lookup
  178. Guo Y, Wang Y, Cao L, Wang P, Qing J, Zheng Q, Shang L, Yin Z, Sun Y. A Conserved Inhibitory Mechanism of a Lycorine Derivative against Enterovirus and Hepatitis C Virus.. Antimicrob Agents Chemother 2016 Feb;60(2):913-24.
    doi: 10.1128/AAC.02274-15pmc: PMC4750679pubmed: 26596952google scholar: lookup
  179. Lin SC, Lehman CW, Stewart AK, Panny L, Bracci N, Wright JLC, Paige M, Strangman WK, Kehn-Hall K. Homoseongomycin, a compound isolated from marine actinomycete bacteria K3-1, is a potent inhibitor of encephalitic alphaviruses.. Antiviral Res 2021 Jul;191:105087.
    doi: 10.1016/j.antiviral.2021.105087pubmed: 33965437google scholar: lookup
  180. Karpenko I, Deev S, Kiselev O, Charushin V, Rusinov V, Ulomsky E, Deeva E, Yanvarev D, Ivanov A, Smirnova O, Kochetkov S, Chupakhin O, Kukhanova M. Antiviral properties, metabolism, and pharmacokinetics of a novel azolo-1,2,4-triazine-derived inhibitor of influenza A and B virus replication.. Antimicrob Agents Chemother 2010 May;54(5):2017-22.
    doi: 10.1128/AAC.01186-09pmc: PMC2863629pubmed: 20194696google scholar: lookup
  181. Sapozhnikova I.M., Ulomsky E.N., Rusinov V.L., Chupakhin O.N., Stepanov A.V., Savateeva-Lyubimova T.N., Sivak K.V.. 3-Cyanoazolo [5,1-c][1,2,4]triazines: Synthesis and antiviral activity. Chem. Heterocycl. Comp. 2021;57:467–472.
    doi: 10.1007/s10593-021-02925-3google scholar: lookup
  182. Sindac JA, Barraza SJ, Dobry CJ, Xiang J, Blakely PK, Irani DN, Keep RF, Miller DJ, Larsen SD. Optimization of novel indole-2-carboxamide inhibitors of neurotropic alphavirus replication.. J Med Chem 2013 Nov 27;56(22):9222-41.
    doi: 10.1021/jm401330rpmc: PMC3895407pubmed: 24151954google scholar: lookup
  183. Barraza SJ, Sindac JA, Dobry CJ, Delekta PC, Lee PH, Miller DJ, Larsen SD. Synthesis and biological activity of conformationally restricted indole-based inhibitors of neurotropic alphavirus replication: Generation of a three-dimensional pharmacophore.. Bioorg Med Chem Lett 2021 Aug 15;46:128171.
    doi: 10.1016/j.bmcl.2021.128171pmc: PMC8272561pubmed: 34098081google scholar: lookup
  184. Saul S, Huang PT, Einav S, Asquith CRM. Identification and evaluation of 4-anilinoquin(az)olines as potent inhibitors of both dengue virus (DENV) and Venezuelan equine encephalitis virus (VEEV).. Bioorg Med Chem Lett 2021 Nov 15;52:128407.
    doi: 10.1016/j.bmcl.2021.128407pubmed: 34624490google scholar: lookup
  185. Huang PT, Saul S, Einav S, Asquith CRM. Optimization of 4-Anilinoquinolines as Dengue Virus Inhibitors.. Molecules 2021 Dec 3;26(23).
    doi: 10.3390/molecules26237338pmc: PMC8659069pubmed: 34885921google scholar: lookup
  186. NIAID NIAID Emerging Infectious Diseases/Pathogens | Category B Pathogens. [(accessed on 31 January 2023)]; Available online: https://www.niaid.nih.gov/research/emerging-infectious-diseases-pathogens.
  187. Villari P, Spielman A, Komar N, McDowell M, Timperi RJ. The economic burden imposed by a residual case of eastern encephalitis.. Am J Trop Med Hyg 1995 Jan;52(1):8-13.
    doi: 10.4269/ajtmh.1995.52.8pubmed: 7856830google scholar: lookup
  188. Earnest MP, Goolishian HA, Calverley JR, Hayes RO, Hill HR. Neurologic, intellectual, and psychologic sequelae following western encephalitis. A follow-up study of 35 cases.. Neurology 1971 Sep;21(9):969-74.
    doi: 10.1212/WNL.21.9.969pubmed: 5106260google scholar: lookup
  189. Allio T. The FDA Animal Rule and its role in protecting human safety.. Expert Opin Drug Saf 2018 Oct;17(10):971-973.
    doi: 10.1080/14740338.2018.1518429pubmed: 30198799google scholar: lookup
  190. Aebersold P. FDA Experience with Medical Countermeasures under the Animal Rule.. Adv Prev Med 2012;2012:507571.
    doi: 10.1155/2012/507571pmc: PMC3177089pubmed: 21991452google scholar: lookup
  191. Painter GR, Natchus MG, Cohen O, Holman W, Painter WP. Developing a direct acting, orally available antiviral agent in a pandemic: the evolution of molnupiravir as a potential treatment for COVID-19.. Curr Opin Virol 2021 Oct;50:17-22.
    doi: 10.1016/j.coviro.2021.06.003pmc: PMC8277160pubmed: 34271264google scholar: lookup
  192. Jonsson CB, Golden JE, Meibohm B. Time to 'Mind the Gap' in novel small molecule drug discovery for direct-acting antivirals for SARS-CoV-2.. Curr Opin Virol 2021 Oct;50:1-7.
    doi: 10.1016/j.coviro.2021.06.008pmc: PMC8238655pubmed: 34256351google scholar: lookup
  193. Morens DM, Folkers GK, Fauci AS. Eastern Equine Encephalitis Virus - Another Emergent Arbovirus in the United States.. N Engl J Med 2019 Nov 21;381(21):1989-1992.
    doi: 10.1056/NEJMp1914328pubmed: 31747726google scholar: lookup

Citations

This article has been cited 5 times.
  1. Williams EP, Xue Y, Yang D, Lee J, Kim E, Ponce-Flores A, Zalduondo L, Cao X, Chung D, Golden JE, Meibohm B, Fitzpatrick EA, Weaver SC, Jonsson CB. Broad spectrum antiviral BDGR-164 provides protection against lethal neurotropic alphavirus infection in mice. Antiviral Res 2025 Aug;240:106206.
    doi: 10.1016/j.antiviral.2025.106206pubmed: 40456491google scholar: lookup
  2. Verwimp S, Wagoner J, Arenas EG, De Coninck L, Abdelnabi R, Hyde JL, Schiffer JT, White JM, Matthijnssens J, Neyts J, Polyak SJ, Delang L. Combinations of approved oral nucleoside analogues confer potent suppression of alphaviruses in vitro and in vivo. bioRxiv 2025 Mar 11;.
    doi: 10.1101/2025.01.24.633564pubmed: 39896535google scholar: lookup
  3. VanderGiessen M, de Jager C, Leighton J, Xie H, Theus M, Johnson E, Kehn-Hall K. Neurological manifestations of encephalitic alphaviruses, traumatic brain injuries, and organophosphorus nerve agent exposure. Front Neurosci 2024;18:1514940.
    doi: 10.3389/fnins.2024.1514940pubmed: 39734493google scholar: lookup
  4. Gonçalves SMC, Galdino LV, Lima MC, da Silva Moura JA, Viana DCF, da Rosa MM, Ferreira LFGR, Hernandes MZ, Pereira MC, de Melo Rêgo MJB, da Rocha Pitta I, de Oliveira França R, da Rocha Pitta MG, da Rocha Pitta MG. Evaluation of Thiazolidine Derivatives with Potential Anti-ZIKV Activity. Curr Top Med Chem 2024;24(25):2224-2237.
    doi: 10.2174/0115680266315388240801053401pubmed: 39136505google scholar: lookup
  5. Cao X, Yang D, Parvathareddy J, Chu YK, Kim EJ, Fitz-Henley JN, Li X, Lukka PB, Parmar KR, Temrikar ZH, Dhole P, Adcock RS, Gabbard J, Bansal S, Lee J, Zalduondo L, Hayes E, Stabenow J, Meibohm B, Fitzpatrick EA, Bailey K, Campos RK, Julander JG, Rossi SL, Chung D, Jonsson CB, Golden JE. Efficacy of a brain-penetrant antiviral in lethal Venezuelan and eastern equine encephalitis mouse models. Sci Transl Med 2023 Apr 12;15(691):eabl9344.
    doi: 10.1126/scitranslmed.abl9344pubmed: 37043558google scholar: lookup
Subscribe to our newsletter
Join 99,658 horse owners like you who receive our email updates on horse health and nutrition.