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Literature for peptidase C09.001: sindbis virus-type nsP2 peptidase

Summary Alignment Tree Sequences Sequence features Distribution Structure Literature Substrates Inhibitors

(Topics flags: S Structure, A Assay, P Specificity, I Inhibitor, E Expression, V Review. To select only the references relevant to a single topic, click the link above. See explanation.)

    2026
  1. Sears,J.D., Popov,K.I., Sylvester,P.A., Dickmander,R., Diaz,J., Chang,C.K., Huff,J., Sanders,W., Saba,N.A., Sorensen,M., Drobish,A.M., May,N.A., Namitz,K., Fecko,J., Yennawar,N.H., Morrison,T.E., Tropsha,A., Heise,M.T. and Moorman,N.J.
    Novel computational pipeline to identify target sites for broad spectrum antiviral drugs
    Antiviral Res (2026) 245, 106322-106322. PubMed  Europe PubMed DOI
    2. 2025
  2. Dansana,J., Purohit,P., Panda,M. and Meher,B.R.
    Recent advances in phytocompounds as potential Chikungunya virus non-structural protein 2 protease antagonists: A systematic review
    Phytomedicine (2025) 136, 156359-156359. PubMed  Europe PubMed DOI
  3. Ghoshal,A., Tse,E.G., Hossain,M.A., Asressu,K.H., Merten,E.M., Sears,J.D., Howell,S., Perveen,S., Burdick,J., Morales,N.L., Martinez,S.A., Law,I., Davenport,B.J., Morrison,T.E., Streblow,Z.J., Streblow,D.N., Mordant,A.L., Webb,T.S., Cabrera,A., Herring,L.E., Arrowsmith,C.H., Pearce,K.H., Moorman,N.J., Heise,M.T., Counago,R.M., Brown,P.J. and Willson,T.M.
    A covalent chemical probe for Chikungunya nsP2 cysteine protease with antialphaviral activity and proteome-wide selectivity
    Sci Rep (2025) 15, 7264-7264. PubMed  Europe PubMed DOI  PMC  EPMC
  4. Ghoshal,A., Sears,J.D., Hossain,M.A., Tse,E.G., Howell,S., Burdick,J.E., Morales,N.L., Martinez,S.A., Law,I., Streblow,Z.J., Streblow,D.N., Counago,R.M., Moorman,N.J., Heise,M.T. and Willson,T.M.
    N-Alkyl Sulfamates as a New Class of nsP2 Cysteine Protease Inhibitors with Broad-Spectrum Antialphaviral Activity
    J Med Chem (2025) PubMed  Europe PubMed DOI  I
  5. Gurunathan,R.S., Rajaram,A., Chandrabose,S. and Singh,S.K.
    Decoding pH-dependent structural dynamics of CHIKV nsP2 protease: insights from computational antiviral targeting
    Mol Divers (2025) PubMed  Europe PubMed DOI
  6. He,J., Illingworth,H., Ullrich,S., Ghosh,P., Ton,J., Jackson,C.J. and Nitsche,C.
    Synthesis, screening and validation of cysteine-reactive fragments as chikungunya virus protease inhibitors
    Bioorg Med Chem Lett (2025) 122, 130176-130176. PubMed  Europe PubMed DOI
  7. Li,S., Hu,X., Ahn,Y.M., Medina,A., Ye,L., Heffner,A., Messing,S., Denson,J.P., Esposito,D., Lee,E.M. and Martinez,N.J.
    A quantitative high-throughput screening pipeline to identify small molecule inhibitors of Chikungunya nsP2 protease
    Sci Rep (2025) 15, 33479-33479. PubMed  Europe PubMed DOI  PMC  EPMC
  8. Makhaik,S., Rut,W., Choudhary,S., Upadhyay,T., Hao,C., Westberg,M., Bobst,C., Yoo,E., Fejzo,J., Lin,M.Z., Bogyo,M., Thompson,P., Drag,M. and Hardy,J.A.
    A robust fluorogenic substrate for chikungunya virus protease (nsP2) activity
    Protein Sci (2025) 34, e70069-e70069. PubMed  Europe PubMed DOI  PMC  EPMC
  9. Makhaik,S., Rut,W., Choudhary,S., Upadhyay,T., Hao,C., Westberg,M., Bobst,C., Yoo,E., Fejzo,J., Lin,M.Z., Bogyo,M., Thompson,P., Drag,M. and Hardy,J.A.
    A Robust Fluorogenic Substrate for Chikungunya Virus Protease (nsP2) Activity
    bioRxiv (2025) PubMed  Europe PubMed DOI  PMC  EPMC
  10. Mastalipour,M., Gering,I., Coronado,M.A., Gonzalez,J.E.H., Willbold,D. and Eberle,R.J.
    Novel peptide inhibitor for the Chikungunya virus nsP2 protease: Identification and characterization
    Curr Res Microb Sci (2025) 8, 100376-100376. PubMed  Europe PubMed DOI  PMC  EPMC  I
  11. Padilha,E.K.A., da Silva,J.C.S. and Silva-Junior,E.F.D.
    Revealing the water-catalyzed activation of Chikungunya virus non-structural protein 2 (nsP2)
    J Mol Graph Model (2025) 140, 109129-109129. PubMed  Europe PubMed DOI
    12. 2024
  12. Ghoshal,A., Asressu,K.H., Hossain,M.A., Brown,P.J., Nandakumar,M., Vala,A., Merten,E.M., Sears,J.D., Law,I., Burdick,J.E., Morales,N.L., Perveen,S., Pearce,K.H., Popov,K.I., Moorman,N.J., Heise,M.T. and Willson,T.M.
    Structure Activity of beta-Amidomethyl Vinyl Sulfones as Covalent Inhibitors of Chikungunya nsP2 Cysteine Protease with Antialphavirus Activity
    J Med Chem (2024) PubMed  Europe PubMed DOI  I
  13. Ghoshal,A., Tse,E.G., Hossain,M.A., Asressu,K.H., Merten,E.M., Sears,J.D., Howell,S., Perveen,S., Burdick,J., Morales,N.L., Martinez,S.A., Law,I., Davenport,B.J., Morrison,T.E., Streblow,Z.J., Streblow,D.N., Mordant,A.L., Webb,T.S., Cabrera,A., Herring,L.E., Arrowsmith,C.H., Pearce,K.H., Moorman,N.J., Heise,M.T., Counago,R.M., Brown,P.J. and Willson,T.M.
    A Covalent Chemical Probe for Chikungunya nsP2 Cysteine Protease with Antialphaviral Activity and Proteome-wide Selectivity
    Res Sq (2024) PubMed  Europe PubMed DOI  PMC  EPMC
  14. Merten,E.M., Sears,J.D., Leisner,T.M., Hardy,P.B., Ghoshal,A., Hossain,M.A., Asressu,K.H., Brown,P.J., Tse,E.G., Stashko,M.A., Li,K., Norris-Drouin,J.L., Herring,L.E., Mordant,A.L., Webb,T.S., Mills,C.A., Barker,N.K., Streblow,Z.J., Perveen,S., Arrowsmith,C.H., Counago,R.M., Arnold,J.J., Cameron,C.E., Streblow,D.N., Moorman,N.J., Heise,M.T., Willson,T.M., Popov,K.I. and Pearce,K.H.
    Identification of a cell-active chikungunya virus nsP2 protease inhibitor using a covalent fragment-based screening approach
    Proc Natl Acad Sci U S A (2024) 121, e2409166121-e2409166121. PubMed  Europe PubMed DOI  I
  15. Merten,E.M., Sears,J.D., Leisner,T.M., Hardy,P.B., Ghoshal,A., Hossain,M.A., Asressu,K.H., Brown,P.J., Stashko,M.A., Herring,L.E., Mordant,A.L., Webb,T.S., Mills,C.A., Barker,N.K., Arnold,J.J., Cameron,C.E., Streblow,D.N., Moorman,N.J., Heise,M., Willson,T.M., Popov,K.I. and Pearce,K.H.
    Discovery of a cell-active chikungunya virus nsP2 protease inhibitor using a covalent fragment-based screening approach
    bioRxiv (2024) PubMed  Europe PubMed DOI  PMC  EPMC  I
  16. Metibemu,D.S., Adeyinka,O.S., Falode,J., Hampton,T., Crown,O., Ojobor,J.C., Narayanan,A., Julander,J. and Ogungbe,I.V.
    Inhibitor of the non-structural protein 2 protease shows promising efficacy in mouse models of chikungunya
    Eur J Med Chem (2024) 278, 116808-116808. PubMed  Europe PubMed DOI  I
  17. Rabelo,V.W., Sanchez-Nunez,M.L., Correa-Amorim,L.S., Kuhn,R.J., Abreu,P.A. and Paixao,I.C.N.P.
    In Silico Drug Repurposing Uncovered the Antiviral Potential of the Antiparasitic Drug Oxibendazole Against the Chikungunya Virus
    ACS Omega (2024) 9, 27632-27642. PubMed  Europe PubMed DOI  PMC  EPMC
  18. Sharma,K.B., Subramani,C., Ganesh,K., Sharma,A., Basu,B., Balyan,S., Sharma,G., Ka,S., Deb,A., Srivastava,M., Chugh,S., Sehrawat,S., Bharadwaj,K., Rout,A., Sahoo,P.K., Saurav,S., Motiani,R.K., Singh,R., Jain,D., Asthana,S., Wadhwa,R. and Vrati,S.
    Withaferin A inhibits Chikungunya virus nsP2 protease and shows antiviral activity in the cell culture and mouse model of virus infection
    PLoS Pathog (2024) 20, e1012816-e1012816. PubMed  Europe PubMed DOI  PMC  EPMC  I
    19. 2023
  19. Souza,B.G., Choudhary,S., Vilela,G.G., Passos,G.F.S., Costa,C.A.C.B., Freitas,J.D., Coelho,G.L., Brandao,J.A., Anderson,L., Bassi,E.J., Araujo-Junior,J.X., Tomar,S. and Silva-Junior,E.F.D.
    Design, synthesis, antiviral evaluation, and In silico studies of acrylamides targeting nsP2 from Chikungunya virus
    Eur J Med Chem (2023) 258, 115572-115572. PubMed  Europe PubMed DOI  I
    20. 2022
  20. De,S., Ghosh,S., Keshry,S.S., Mahish,C., Mohapatra,C., Guru,A., Mamidi,P., Datey,A., Pani,S.S., Vasudevan,D., Beuria,T.K., Chattopadhyay,S., Subudhi,B.B. and Chattopadhyay,S.
    MBZM-N-IBT, a Novel Small Molecule, Restricts Chikungunya Virus Infection by Targeting nsP2 Protease Activity In Vitro, In Vivo, and Ex Vivo
    Antimicrob Agents Chemother (2022) 66, e0046322-e0046322. PubMed  Europe PubMed DOI  PMC  EPMC
  21. Laurent,T., Kumar,P., Liese,S., Zare,F., Jonasson,M., Carlson,A. and Carlson,L.A.
    Architecture of the chikungunya virus replication organelle
    elife (2022) 11 PubMed  Europe PubMed DOI  PMC  EPMC
  22. Rabelo,V.W., de Palmer Paixao,I.C.N. and Abreu,P.A.
    Structural insights into the inhibition of the nsP2 protease from Chikungunya virus by molecular modeling approaches
    J Mol Model (2022) 28, 311-311. PubMed  Europe PubMed DOI
    23. 2021
  23. Ivanova,L., Rausalu,K., Zusinaite,E., Tammiku-Taul,J., Merits,A. and Karelson,M.
    1,3-Thiazolbenzamide Derivatives as Chikungunya Virus nsP2 Protease Inhibitors
    ACS Omega (2021) 6, 5786-5794. PubMed  Europe PubMed DOI  PMC  EPMC  I
  24. Ivanova,L., Rausalu,K., Oseka,M., Kananovich,D.G., Zusinaite,E., Tammiku-Taul,J., Lopp,M., Merits,A. and Karelson,M.
    Novel Analogues of the Chikungunya Virus Protease Inhibitor: Molecular Design, Synthesis, and Biological Evaluation
    ACS Omega (2021) 6, 10884-10896. PubMed  Europe PubMed DOI  PMC  EPMC
    25. 2020
  25. Fazal,F., Anwar,T., Waheed,Y. and Parvaiz,F.
    Prediction of promiscuous epitopes in NSP2 of Chikungunya virus: An in-silico approach
    Trop Biomed (2020) 37, 566-577. PubMed  Europe PubMed DOI
  26. Law,Y.S., Wang,S., Tan,Y.B., Shih,O., Utt,A., Goh,W.Y., Lian,B.J., Chen,M.W., Jeng,U.S., Merits,A. and Luo,D.
    Inter-domain Flexibility of Chikungunya Virus nsP2 Helicase-Protease Differentially Influences Viral RNA Replication and Infectivity
    J Virol (2020) PubMed  Europe PubMed DOI
    27. 2019
  27. Kumar,P., Kumar,D. and Giri,R.
    Targeting the nsp2 cysteine protease of Chikungunya virus using FDA approved library and selected cysteine protease inhibitors
    Pathogens (2019) 8 PubMed  Europe PubMed DOI
    28. 2018
  28. Lulla,V., Karo-Astover,L., Rausalu,K., Saul,S., Merits,A. and Lulla,A.
    Timeliness of proteolytic events is prerequisite for efficient functioning of the alphaviral replicase
    J Virol (2018) 92, e00151-18-e00151-18. PubMed  Europe PubMed DOI
  29. Narwal,M., Singh,H., Pratap,S., Malik,A., Kuhn,R.J., Kumar,P. and Tomar,S.
    Crystal structure of chikungunya virus nsP2 cysteine protease reveals a putative flexible loop blocking its active site
    Int J Biol Macromol (2018) 116, 451-462. PubMed  Europe PubMed DOI  A  S
  30. Ramphan,S., Khongwichit,S., Saisawang,C., Kovanich,D., Ketterman,A.J., Ubol,S., Auewarakul,P., Roytrakul,S., Smith,D.R. and Kuadkitkan,A.
    Ubiquitin-conjugating enzyme E2 L3 is downregulated by the Chikungunya virus nsP2 protease
    Proteomics Clin Appl (2018) 12, e1700020-e1700020. PubMed  Europe PubMed DOI
  31. Saha,A., Acharya,B.N., Priya,R., Tripathi,N.K., Shrivastava,A., Rao,M.K., Kesari,P., Narwal,M., Tomar,S., Bhagyawant,S.S., Parida,M. and Dash,P.K.
    Development of nsP2 protease based cell free high throughput screening assay for evaluation of inhibitors against emerging Chikungunya virus
    Sci Rep (2018) 8, 10831-10831. PubMed  Europe PubMed DOI  PMC  EPMC  A  I
  32. Singh,H., Mudgal,R., Narwal,M., Kaur,R., Singh,V.A., Malik,A., Chaudhary,M. and Tomar,S.
    Chikungunya virus inhibition by peptidomimetic inhibitors targeting virus-specific cysteine protease
    Biochimie (2018) 149, 51-61. PubMed  Europe PubMed DOI  A
    33. 2017
  33. Dhindwal,S., Kesari,P., Singh,H., Kumar,P. and Tomar,S.
    Conformer and pharmacophore based identification of peptidomimetic inhibitors of Chikungunya virus nsP2 protease
    J Biomol Struct Dyn (2017) 35, 3522-3539. PubMed  Europe PubMed DOI  I
  34. Ramakrishnan,C., Kutumbarao,N.H.V., Suhitha,S. and Velmurugan,D.
    Structure-function relationship of Chikungunya nsP2 protease: a comparative study with papain
    Chem Biol Drug Des (2017) 89, 772-782. PubMed  Europe PubMed DOI  S
  35. Saisawang,C., Kuadkitkan,A., Smith,D.R., Ubol,S. and Ketterman,A.J.
    Glutathionylation of chikungunya nsP2 protein affects protease activity
    Biochim Biophys Acta (2017) 1861, 106-111. PubMed  Europe PubMed DOI
    36. 2016
  36. Byler,K.G., Collins,J.T., Ogungbe,I.V. and Setzer,W.N.
    Alphavirus protease inhibitors from natural sources: a homology modeling and molecular docking investigation
    Comput Biol Chem (2016) 64, 163-184. PubMed  Europe PubMed DOI  I
  37. Das,P.K., Puusepp,L., Varghese,F.S., Utt,A., Ahola,T., Kananovich,D.G., Lopp,M., Merits,A. and Karelson,M.
    Design and validation of novel chikungunya virus protease inhibitors
    Antimicrob Agents Chemother (2016) 60, 7382-7395. PubMed  Europe PubMed DOI  I
  38. Rausalu,K., Utt,A., Quirin,T., Varghese,F.S., Zusinaite,E., Das,P.K., Ahola,T. and Merits,A.
    Chikungunya virus infectivity, RNA replication and non-structural polyprotein processing depend on the nsP2 protease's active site cysteine residue
    Sci Rep (2016) 6, 37124-37124. PubMed  Europe PubMed DOI  P
    39. 2015
  39. Agarwal,T., Asthana,S. and Bissoyi,A.
    Molecular modeling and docking study to elucidate novel Chikungunya virus nsP2 protease inhibitors
    Indian J Pharm Sci (2015) 77, 453-460. PubMed  Europe PubMed  PMC  EPMC  I
  40. El-Labbad,E.M., Ismail,M.A., Abou Ei Ella,D.A., Ahmed,M., Wang,F., Barakat,K.H. and Abouzid,K.A.
    Discovery of novel peptidomimetics as irreversible CHIKV nsP2 protease inhibitors using quantum mechanical-based ligand descriptors
    Chem Biol Drug Des (2015) 86, 1518-1527. PubMed  Europe PubMed DOI  I
  41. Jadav,S.S., Sinha,B.N., Hilgenfeld,R., Pastorino,B., de Lamballerie,X. and Jayaprakash,V.
    Thiazolidone derivatives as inhibitors of chikungunya virus
    Eur J Med Chem (2015) 89, 172-178. PubMed  Europe PubMed DOI  I
  42. Nguyen,P.T., Yu,H. and Keller,P.A.
    Identification of chikungunya virus nsP2 protease inhibitors using structure-base approaches
    J Mol Graph Model (2015) 57C, 1-8. PubMed  Europe PubMed DOI  I
  43. Saisawang,C., Saitornuang,S., Sillapee,P., Ubol,S., Smith,D.R. and Ketterman,A.J.
    Chikungunya nsP2 protease is not a papain-like cysteine protease and the catalytic dyad cysteine is interchangeable with a proximal serine
    Sci Rep (2015) 5, 17125-17125. PubMed  Europe PubMed DOI  PMC  EPMC
  44. Saisawang,C., Sillapee,P., Sinsirimongkol,K., Ubol,S., Smith,D.R. and Ketterman,A.J.
    Full length and protease domain activity of chikungunya virus nsP2 differ from other alphavirus nsP2 proteases in recognition of small peptide substrates
    Biosci Rep (2015) 35 PubMed  Europe PubMed DOI  PMC  EPMC  P
    45. 2013
  45. Bassetto,M., De Burghgraeve,T., Delang,L., Massarotti,A., Coluccia,A., Zonta,N., Gatti,V., Colombano,G., Sorba,G., Silvestri,R., Tron,G.C., Neyts,J., Leyssen,P. and Brancale,A.
    Computer-aided identification, design and synthesis of a novel series of compounds with selective antiviral activity against chikungunya virus
    Antiviral Res (2013) 98, 12-18. PubMed  Europe PubMed DOI  I
  46. Lulla,V., Karo-Astover,L., Rausalu,K., Merits,A. and Lulla,A.
    Presentation overrides specificity: probing the plasticity of alphaviral proteolytic activity through mutational analysis
    J Virol (2013) 87, 10207-10220. PubMed  Europe PubMed DOI  P
    47. 2012
  47. Bora,L.
    Homology modeling and docking to potential novel inhibitor for Chikungunya (37997) protein nsP2 protease
    J Proteomics Bioinformatics (2012) 5, 54-59. DOI
  48. Lulla,A., Lulla,V. and Merits,A.
    Macromolecular assembly-driven processing of the 2/3 cleavage site in the alphavirus replicase polyprotein
    J Virol (2012) 86, 553-565. PubMed  Europe PubMed DOI
  49. Shin,G., Yost,S.A., Miller,M.T., Elrod,E.J., Grakoui,A. and Marcotrigiano,J.
    Structural and functional insights into alphavirus polyprotein processing and pathogenesis
    Proc Natl Acad Sci U S A (2012) 109, 16534-16539. PubMed  Europe PubMed DOI
  50. Singh,K., Kirubakaran,P., Nagarajan,S., Sakkiah,S., Muthusamy,K., Velmurgan,D. and Jeyakanthan,J.
    Homology modeling, molecular dynamics, e-pharmacophore mapping and docking study of Chikungunya virus nsP2 protease
    J Mol Model (2012) 18, 39-51. PubMed  Europe PubMed DOI  S
  51. Strauss,E.G. and Strauss,J.H.
    Sindbis virus nsP2 endopeptidase
    [ISSN:978-0-12-407743-0] (2012) 3, 2234-2236. DOI
    52. 2009
  52. Zhang,D., Tozser,J. and Waugh,D.S.
    Molecular cloning, overproduction, purification and biochemical characterization of the p39 nsp2 protease domains encoded by three alphaviruses
    Protein Expr Purif (2009) 64, 89-97. PubMed  Europe PubMed DOI  PMC  EPMC  E
    53. 2008
  53. Pastorino,B.A., Peyrefitte,C.N., Almeras,L., Grandadam,M., Rolland,D., Tolou,H.J. and Bessaud,M.
    Expression and biochemical characterization of nsP2 cysteine protease of Chikungunya virus
    Virus Res (2008) 131, 293-298. PubMed  Europe PubMed DOI
    54. 2006
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    Characterization of the cysteine protease domain of Semliki Forest virus replicase protein nsP2 by in vitro mutagenesis
    FEBS Lett (20-2-2006) 580, 1502-1508. PubMed  Europe PubMed DOI  I
  55. Lulla,A., Lulla,V., Tints,K., Ahola,T. and Merits,A.
    Molecular determinants of substrate specificity for Semliki Forest virus nonstructural protease
    J Virol (2006) 80, 5413-5422. PubMed  Europe PubMed DOI  PMC  EPMC  P
    56. 2004
  56. Strauss,E.G. and Strauss,J.H.
    Sindbis virus nsP2 endopeptidase
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    57. 2003
  57. [YEAR:24-10-2003]Vasiljeva,L., Merits,A., Golubtsov,A., Sizemskaja,V., Kaariainen,L. and Ahola,T.
    Regulation of the sequential processing of Semliki Forest virus replicase polyprotein
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    58. 2001
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    Proteolytic processing of Semliki Forest virus-specific non-structural polyprotein by nsP2 protease
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    Site-specific protease activity of the carboxyl-terminal domain of Semliki Forest virus replicase protein nsP2
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    60. 1999
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    Aura virus is a New World representative of Sindbis-like viruses
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    Identification of the active site residues in the nsP2 proteinase of sindbis virus
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    Putative papain-related thiol proteases of positive-strand RNA viruses. Identification of rubi- and aphthovirus proteases and delineation of a novel conserved domain associated with proteases of rubi-, alpha- and coronaviruses
    FEBS Lett (1991) 288, 201-205. PubMed  Europe PubMed DOI
    65. 1990
  65. de Groot,R.J., Hardy,W.R., Shirako,Y. and Strauss,J.H.
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    EMBO J (1990) 9, 2631-2638. PubMed  Europe PubMed  PMC  EPMC  P
  66. Hardy,W.R., Hahn,Y.S., de Groot,R.J., Strauss,E.G. and Strauss,J.H.
    Synthesis and processing of the nonstructural polyproteins of several temperature-sensitive mutants of Sindbis virus
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    67. 1989
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    Evidence that sindbis virus NSP2 is an autoprotease which processes the virus nonstructural polyprotein
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    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) 63, 4653-4664. PubMed  Europe PubMed  PMC  EPMC
    69. 1988
  69. Hardy,W.R. and Strauss,J.H.
    Processing the nonstructural polyproteins of Sindbis virus: study of the kinetics in vivo by using monospecific antibodies
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    70. 1981
  70. Rice,C.M. and Strauss,J.H.
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