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

Summary Alignment Tree Sequences Sequence features Distribution Structure Literature Substrates

(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

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

2025

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
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
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
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
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
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
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
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
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
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

2024

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
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
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
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
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
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
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

2023

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

2022

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
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
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

2021

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
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

2020

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
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

2019

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

2018

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
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
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
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
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

2017

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
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
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

2016

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
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
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

2015

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
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
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
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
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
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

2013

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
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

2012

Bora,L. Homology modeling and docking to potential novel inhibitor for Chikungunya (37997) protein nsP2 protease J Proteomics Bioinformatics (2012) 5, 54-59. DOI
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
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
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
Strauss,E.G. and Strauss,J.H. Sindbis virus nsP2 endopeptidase [ISSN:978-0-12-407743-0] (2012) 3, 2234-2236. DOI

2009

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

2008

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

2006

[YEAR:20-2-2006]Golubtsov,A., Kaariainen,L. and Caldentey,J. 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
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

2004

Strauss,E.G. and Strauss,J.H. Sindbis virus nsP2 endopeptidase [ISSN:0-12-079610-4] (2004) 2, 1269-1271. V

2003

[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 J Biol Chem (24-10-2003) 278, 41636-41645. PubMed Europe PubMed DOI

2001

Merits,A., Vasiljeva,L., Ahola,T., Kaariainen,L. and Auvinen,P. Proteolytic processing of Semliki Forest virus-specific non-structural polyprotein by nsP2 protease J Gen Virol (2001) 82, 765-773. PubMed Europe PubMed
[YEAR:17-8-2001]Vasiljeva,L., Valmu,L., Kaariainen,L. and Merits,A. Site-specific protease activity of the carboxyl-terminal domain of Semliki Forest virus replicase protein nsP2 J Biol Chem (17-8-2001) 276, 30786-30793. PubMed Europe PubMed DOI

1999

Ten Dam,E., Flint,M. and Ryan,M.D. Virus-encoded proteinases of the Togaviridae J Gen Virol (1999) 80, 1879-1888. PubMed Europe PubMed

1995

Rumenapf,T., Strauss,E.G. and Strauss,J.H. Aura virus is a New World representative of Sindbis-like viruses Virology (1995) 208, 621-633. PubMed Europe PubMed DOI

1994

Lemm,J.A., Rumenapf,T., Strauss,E.G., Strauss,J.H. and Rice,C.M. Polypeptide requirements for assembly of functional Sindbis virus replication complexes: a model for the temporal regulation of minus- and plus-strand RNA synthesis EMBO J (1994) 13, 2925-2934. PubMed Europe PubMed PMC EPMC

1992

Strauss,E.G., de Groot,R.J., Levinson,R. and Strauss,J.H. Identification of the active site residues in the nsP2 proteinase of sindbis virus Virology (1992) 191, 932-940. PubMed Europe PubMed DOI

1991

Gorbalenya,A.E., Koonin,E.V. and Lai,M.M.C. 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

1990

de Groot,R.J., Hardy,W.R., Shirako,Y. and Strauss,J.H. Cleavage-site preferences of sindbis virus polyproteins containing the non-structural proteinase. Evidence for temporal regulation of polyprotein processing in vivo EMBO J (1990) 9, 2631-2638. PubMed Europe PubMed PMC EPMC P
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 Virology (1990) 177, 199-208. PubMed Europe PubMed DOI

1989

Ding,M.X. and Schlesinger,M.J. Evidence that sindbis virus NSP2 is an autoprotease which processes the virus nonstructural polyprotein Virology (1989) 171, 280-284. PubMed Europe PubMed
Hardy,W.R. and Strauss,J.H. 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

1988

Hardy,W.R. and Strauss,J.H. Processing the nonstructural polyproteins of Sindbis virus: study of the kinetics in vivo by using monospecific antibodies J Virol (1988) 62, 998-1007. PubMed Europe PubMed PMC EPMC

1981

Rice,C.M. and Strauss,J.H. Nucleotide sequence of the 26S mRNA of Sindbis virus and deduced sequence of the encoded virus structural proteins Proc Natl Acad Sci U S A (1981) 78, 2062-2066. PubMed Europe PubMed PMC EPMC