Potential of Interferon Lambda as an Inhibitor of SARS-CoV-2

封面

如何引用文章

全文:

开放存取 开放存取
受限制的访问 ##reader.subscriptionAccessGranted##
受限制的访问 订阅存取

详细

The study provides an overview of scientific results on the feasibility of using type III interferons against SARS-CoV-2. We have analyzed data obtained from the PubMed electronic database for the period 2020‒2022. The results of our own studies of pharmacological substances based on recombinant IFN-λ1 and its pegylated form are also presented. Completed and ongoing investigations allow us to position IFN-λ as an effective therapeutic agent against SARS-CoV-2.

作者简介

L. Oleinik

Research Institute of Clinical and Experimental Lymрhology – Branch of Institute of Cytology and Genetics,
Siberian Branch, Russian Academy of Sciences

编辑信件的主要联系方式.
Email: larisaoleynik81@gmail.com
Russia, 630090, Novosibirsk

P. Madonov

Research Institute of Clinical and Experimental Lymрhology – Branch of Institute of Cytology and Genetics,
Siberian Branch, Russian Academy of Sciences

Email: larisaoleynik81@gmail.com
Russia, 630090, Novosibirsk

M. Pykhtina

Research Institute of Clinical and Experimental Lymрhology – Branch of Institute of Cytology and Genetics,
Siberian Branch, Russian Academy of Sciences

Email: larisaoleynik81@gmail.com
Russia, 630090, Novosibirsk

参考

  1. Schneider W.M., Chevillotte M.D., Rice C.M. (2014) Interferon-stimulated genes: a complex web of host defenses. Annu. Rev. Immunol. 32, 513–545.
  2. Totura A.L., Baric R.S. (2012) SARS coronavirus pathogenesis: host innate immune responses and viral antagonism of interferon. Curr. Opin. Virol. 2(3), 264–275.
  3. Andreakos E., Salagianni M., Galani I.E., Koltsida O. (2017) Interferon-lambdas: front-line guardians of immunity and homeostasis in the respiratory tract. Front. Immunol. 8, 1232.
  4. Dellgren C., Gad H.H., Hamming O.J., Melchjorsen J., Hartmann R. (2009) Human interferon-λ3 is a potent member of the type III interferon family. Genes Immun. 10(2), 125–131.
  5. Galani I.E., Triantafyllia V., Eleminiadou E.E., Koltsida O., Stavropoulos A., Manioudaki M., Thanos D., Doyle S.E., Kotenko S.V., Thanopoulou K., Andreakos E. (2017) Interferon-λ mediates nonredundant front-line antiviral protection against influenza virus infection without compromising host fitness. Immunity. 46(5), 875–890.e6.
  6. Donnelly R.P., Kotenko S.V. (2010) Interferon-lambda: a new addition to an old family. J. Interferon Cytokine Res. 30(8), 555–564. https://doi.org/10.1089/jir.2010.0078
  7. Mordstein M., Neugebauer E., Ditt V., Jessen B., Rieger T., Falcone V., Sorgeloos F., Ehl S., Mayer D., Kochs G., Schwemmle M., Günther S., Drosten C., Michiels T., Staeheli P. (2010) Lambda interferon renders epithelial cells of the respiratory and gastrointestinal tracts resistant to viral infections. J. Virol. 84(11), 5670–5677.
  8. Ye L., Schnepf D., Staeheli P. (2019) Interferon-λ orchestrates innate and adaptive mucosal immune responses. Nat. Rev. Immunol. 19(10), 614–625.
  9. Davidson S., McCabe T.M., Crotta S., Gad H.H., Hessel E.M., Beinke S., Hartmann R., Wack A. (2016) IFNλ is a potent anti-influenza therapeutic without the inflammatory side effects of IFNα treatment. EMBO Mol. Med. 8(9), 1099–1112.
  10. Jewell N.A., Cline T., Mertz S.E., Smirnov S.V., Flaño E., Schindler C., Grieves J.L., Durbin R.K., Kotenko S.V., Durbin J.E. (2010) Lambda interferon is the predominant interferon induced by influenza A virus infection in vivo. J. Virol. 84(21), 11515–11522. https://doi.org/10.1128/JVI.01703-09
  11. Znaidia M., Demeret C., van der Werf S., Komarova A.V. (2022) Characterization of SARS-CoV-2 evasion: interferon pathway and therapeutic options. Viruses. 14(6), 1247.
  12. Kumar S., Nyodu R., Maurya V.K., Saxena S.K. (2020) Host immune response and immunobiology of human SARS-CoV-2 infection. In: Coronavirus Disease 2019 (COVID-19). Ed. S. Saxena. Medical Virology: From Pathogenesis to Disease Control. Springer, Singapore. 43–53. https://doi.org/10.1007/978-981-15-4814-7_5
  13. Yuen C.K., Lam J.Y., Wong W.M., Mak L.F., Wang X., Chu H., Cai J.P., Jin D.Y., To K.K., Chan J.F., Yuen K.Y., Kok K.H. (2020) SARS-CoV-2 Nsp13, Nsp14, Nsp15 and Orf6 function as potent interferon antagonists. Emerg. Microbes Infect. 9(1), 1418–1428.
  14. Lei X., Dong X., Ma R., Wang W., Xiao X., Tian Z., Wang C., Wang Y., Li L., Ren L., Guo F., Zhao Z., Zhou Z., Xiang Z., Wang J. (2020) Activation and evasion of type I interferon responses by SARS-CoV-2. Nat. Commun. 11(1), 3810.
  15. Shemesh M., Aktepe T.E., Deerain J.M., McAuley J.L., Audsley M.D., David C.T., Purcell D.F.J., Urin V., Hartmann R., Moseley G.W., Mackenzie J.M., Schreiber G., Harari D. (2021) SARS-CoV-2 suppresses IFNβ production mediated by NSP1, 5, 6, 15, ORF6 and ORF7b but does not suppress the effects of added interferon. PLoS Pathog. 17(8), e1009800.
  16. Kouwaki T., Nishimura T., Wang G., Oshiumi H. (2021) RIG-I-like receptor-mediated recognition of viral genomic RNA of severe acute respiratory syndrome coronavirus-2 and viral escape from the host innate immune responses. Front. Immunol. 12, 700926.
  17. Xia H., Cao Z., Xie X., Zhang X., Chen J.Y., Wang H., Menachery V.D., Rajsbaum R., Shi P.Y. (2020) Evasion of type I interferon by SARS-CoV-2. Cell Rep. 33(1), 108234.
  18. Lokugamage K.G., Hage A., de Vries M., Valero-Jimenez A.M., Schindewolf C., Dittmann M., Rajsbaum R., Menachery V.D. (2020) Type I interferon susceptibility distinguishes SARS-CoV-2 from SARS-CoV. J. Virol. 94(23), e01410-20.
  19. Miorin L., Kehrer T., Sanchez-Aparicio M.T., Zhang K., Cohen P., Patel R.S., Cupic A., Makio T., Mei M., Moreno E., Danziger O., White K.M., Rathnasinghe R., Uccellini M., Gao S., Aydillo T., Mena I., Yin X., Martin-Sancho L., Krogan N.J., Chanda S.K., Schotsaert M., Wozniak R.W., Ren Y., Rosenberg B.R., Fontoura B.M.A., Garcia-Sastre A. (2020) SARS-CoV-2 Orf6 hijacks Nup98 to block STAT nuclear import and antagonize interferon signaling. Proc. Natl. Acad. Sci. USA. 117(45), 28344–28354.
  20. Shin D., Mukherjee R., Grewe D., Bojkova D., Baek K., Bhattacharya A., Schulz L., Widera M., Mehdipour A.R., Tascher G., Geurink P.P., Wilhelm A., van der Heden van Noort G.J., Ovaa H., Müller S., Knobeloch K.P., Rajalingam K., Schulman B.A., Cinatl J., Hummer G., Ciesek S., Dikic I. (2020) Papain-like protease regulates SARS-CoV-2 viral spread and innate immunity. Nature. 587(7835), 657‒662.
  21. Hadjadj J., Yatim N., Barnabei L., Corneau A., Boussier J., Smith N., Pere H., Charbit B., Bondet V., Chenevier-Gobeaux C., Breillat P., Carlier N., Gauzit R., Morbieu C., Pene F., Marin N., Roche N., Szwebel T.A., Merkling S.H., Treluyer J.M., Veyer D., Mouthon L., Blanc C., Tharaux P.L., Rozenberg F., Fischer A., Duffy D., Rieux-Laucat F., Kerneis S., Terrier B. (2020) Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients. Sci-ence. 369(6504), 718‒724.
  22. Blanco-Melo D., Nilsson-Payant B.E., Liu W.C., Uhl S., Hoagland D., Moller R., Jordan T.X., Oishi K., Panis M., Sachs D., Wang T.T., Schwartz R.E., Lim J.K., Albrecht R.A., tenOever B.R. (2020) Imbalanced host response to SARS-CoV2 drives development of COVID-19. Cell. 181(5), 1036–1045.e9.
  23. Schultze J.L., Aschenbrenner A.C. (2021) COVID-19 and the human innate immune system. Cell. 184(7), 1671–1692.
  24. Scagnolari C., Pierangeli A., Frasca F., Bitossi C., Viscido A., Oliveto G., Scordio M., Mazzuti L., Di Carlo D., Gentile M., Solimini A., Ceccarelli G., Pugliese F., Mastroianni C.M., d’Ettorre G., Turriziani O., Antonelli G. (2021) Differential induction of type I and III interferon genes in the upper respiratory tract of patients with coronavirus disease 2019 (COVID-19). Virus Res. 295, 198283.
  25. Bastard P., Orlova E., Sozaeva L., Levy R., James A., Schmitt M.M., Ochoa S., Kareva M., Rodina Y., Gervais A., Le Voyer T., Rosain J., Philippot Q., Neehus A.L., Shaw E., Migaud M., Bizien L., Ekwall O., Berg S., Beccuti G., Ghizzoni L., Thiriez G., Pavot A., Goujard C., Fremond M.L., Carter E., Rothenbuhler A., Linglart A., Mignot B., Comte A., Cheikh N., Hermine O., Breivik L., Husebye E.S., Humbert S., Rohrlich P., Coaquette A., Vuoto F., Faure K., Mahlaoui N., Kotnik P., Battelino T., Trebušak Podkrajšek K., Kisand K., Ferré E.M.N., DiMaggio T., Rosen L.B., Burbelo P.D., McIntyre M., Kann N.Y., Shcherbina A., Pavlova M., Kolodkina A., Holland S.M., Zhang S.Y., Crow Y.J., Notarangelo L.D., Su H.C., Abel L., Anderson M.S., Jouanguy E., Neven B., Puel A., Casanova J.L., Lionakis M.S. (2021) Preexisting autoantibodies to type I IFNs underlie critical COVID-19 pneumonia in patients with APS-1. J. Exp. Med. 218(7), e20210554.
  26. Bastard P., Rosen L.B., Zhang Q., Michailidis E., Hoffmann H.H., Zhang Y., Dorgham K., Philippot Q., Rosain J., Béziat V., Manry J., Shaw E., Haljasmägi L., Peterson P., Lorenzo L., Bizien L., Trouillet-Assant S., Dobbs K., de Jesus A.A., Belot A., Kallaste A., Catherinot E., Tandjaoui-Lambiotte Y., Le Pen J., Kerner G., Bigio B., Seeleuthner Y., Yang R., Bolze A., Spaan A.N., Delmonte O.M., Abers M.S., Aiuti A., Casari G., Lampasona V., Piemonti L., Ciceri F., Bilguvar K., Lifton R.P., Vasse M., Smadja D.M., Migaud M., Hadjadj J., Terrier B., Duffy D., Quintana-Murci L., van de Beek D., Roussel L., Vinh D.C., Tangye S.G., Haerynck F., Dalmau D., Martinez-Picado J., Brodin P., Nussenzweig M.C., Boisson-Dupuis S., Rodríguez-Gallego C., Vogt G., Mogensen T.H., Oler A.J., Gu J., Burbelo P.D., Cohen J.I., Biondi A., Bettini L.R., D’Angio M., Bonfanti P., Rossignol P., Mayaux J., Rieux-Laucat F., Husebye E.S., Fusco F., Ursini M.V., Imberti L., Sottini A., Paghera S., Quiros-Roldan E., Rossi C., Castagnoli R., Montagna D., Licari A., Marseglia G.L., Duval X., Ghosn J., Tsang J.S., Goldbach-Mansky R., Kisand K., Lionakis M.S., Puel A., Zhang S.Y., Holland S.M., Gorochov G., Jouanguy E., Rice C.M., Cobat A., Notarangelo L.D., Abel L., Su H.C., Casanova J.L. (2020) Autoantibodies against type I IFNs in patients with life-threatening COVID-19. Science. 370(6515), eabd4585.
  27. Lucas C., Wong P., Klein J., Castro T.B.R., Silva J., Sundaram M., Ellingson M.K., Mao T., Oh J.E., Israelow B., Takahashi T., Tokuyama M., Lu P., Venkataraman A., Park A., Mohanty S., Wang H., Wyllie A.L., Vogels C.B.F., Earnest R., Lapidus S., Ott I.M., Moore A.J., Muenker M.C., Fournier J.B., Campbell M., Odio C.D., Casanovas-Massana A., Herbst R., Shaw A.C., Medzhitov R., Schulz W.L., Grubaugh N.D., Dela Cruz C., Farhadian S., Ko A.I., Omer S.B., Iwasaki A. (2020) Longitudinal analyses reveal immunological misfiring in severe COVID-19. Nature. 584(7821), 463–469.
  28. Ge D., Fellay J., Thompson A.J., Simon J.S., Shianna K.V., Urban T.J., Heinzen E.L., Qiu P., Bertelsen A.H., Muir A.J., Sulkowski M., McHutchison J.G., Goldstein D.B. (2009) Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature. 461(7262), 399–401.
  29. Suppiah V., Moldovan M., Ahlenstiel G., Berg T., Weltman M., Abate M.L., Bassendine M., Spengler U., Dore G.J., Powell E., Riordan S., Sheridan D., Smedile A., Fragomeli V., Muller T., Bahlo M., Stewart G.J., Booth D.R., George J. (2009) IL28B is associated with response to chronic hepatitis C interferon-α and ribavirin therapy. Nat. Genet. 41(10), 1100–1104.
  30. Tanaka Y., Nishida N., Sugiyama M., Kurosaki M., Matsuura K., Sakamoto N., Nakagawa M., Korenaga M., Hino K., Hige S., Ito Y., Mita E., Tanaka E., Mochida S., Murawaki Y., Honda M., Sakai A., Hiasa Y., Nishiguchi S., Koike A., Sakaida I., Imamura M., Ito K., Yano K., Masaki N., Sugauchi F., Izumi N., Tokunaga K., Mizokami M. (2009) Genome-wide association of IL28B with response to pegylated interferon-α and ribavirin therapy for chronic hepatitis C. Nat. Genet. 41(10), 1105–1109.
  31. Rugwizangoga B., Andersson M.E., Kabayiza J.C., Nilsson M.S., Ármannsdóttir B., Aurelius J., Nilsson S., Hellstrand K., Lindh M., Martner A. (2019) IFNL4 genotypes predict clearance of RNA viruses in Rwandan children with upper respiratory tract infections. Front. Cell Infect. Microbiol. 9, 340.
  32. Saponi-Cortes J.M.R., Rivas M.D., Calle-Alonso F., Sanchez J.F., Costo A., Martin C., Zamorano J. (2021) IFNL4 genetic variant can predispose to COVID-19. Sci. Rep. 11(1), 21185.
  33. Amodio E., Pipitone R.M., Grimaudo S., Immordino P., Maida C.M., Prestileo T., Restivo V., Tramuto F., Vitale F., Craxì A., Casuccio A. (2020) SARS-CoV-2 viral load, IFNλ polymorphisms and the course of COVID-19: an observational study. J. Clin. Med. 9(10), 3315.
  34. Rahimi P., Tarharoudi R., Rahimpour A., Mosayebi Amroabadi J., Ahmadi I., Anvari E., Siadat S.D., Aghasadeghi M., Fateh A. (2021) The association between interferon lambda 3 and 4 gene single-nucleotide polymorphisms and the recovery of COVID-19 patients. Virol. J. 18(1), 221.
  35. Kim H.J., Jo A., Jeon Y.J., An S., Lee K.M., Yoon S.S., Choi J.Y. (2019) Nasal commensal Staphylococcus epidermidis enhances interferon-λ-dependent immunity against influenza virus. Microbiome. 7(1), 80.
  36. Fox J.M., Crabtree J.M., Sage L.K., Tompkins S.M., Tripp R.A. (2015) Interferon lambda upregulates IDO1 expression in respiratory epithelial cells after influenza virus infection. J. Interferon Cytokine Res. 35(7), 554–562.
  37. Iwasaki A., Pillai P.S. (2014) Innate immunity to influenza virus infection. Nat. Rev. Immunol. 14(5), 315–328.
  38. Wang J., Oberley-Deegan R., Wang S., Nikrad M., Funk C.J., Hartshorn K.L., Mason R.J. (2009) Human alveolar type II cells secrete antiviral IL-29 (IFN-λ1) in response to influenza A infection. J. Immunol. 182(3), 1296–1304.
  39. Beucher G., Blondot M.L., Celle A., Pied N., Recordon-Pinson P., Esteves P., Faure M., Métifiot M., Lacomme S., Dacheux D., Robinson D.R., Längst G., Beaufils F., Lafon M.E., Berger P., Landry M., Malvy D., Trian T., Andreola M.L., Wodrich H. (2022) Bronchial epithelia from adults and children: SARS-CoV-2 spread via syncytia formation and type III interferon infectivity restriction. Proc. Natl. Acad. Sci. USA. 119(28), e2202370119.
  40. Wang N., Zhan Y., Zhu L., Hou Z., Liu F., Song P., Qiu F., Wang X., Zou X., Wan D., Qian X., Wang S., Guo Y., Yu H., Cui M., Tong G., Xu Y., Zheng Z., Lu Y., Hong P. (2020) Retrospective multicenter cohort study shows early interferon therapy is associated with favorable clinical responses in COVID-19 patients. Cell Host Microbe. 28(3), 455–464.
  41. Felgenhauer U., Schoen A., Gad H.H., Hartmann R., Schaubmar A.R., Failing K., Drosten C., Weber F. (2020) Inhibition of SARS-CoV-2 by type I and type III interferons. J. Biol. Chem. 295(41), 13958‒13964.
  42. Vanderheiden A., Ralfs P., Chirkova T., Upadhyay A.A., Zimmerman M.G., Bedoya S., Aoued H., Tharp G.M., Pellegrini K.L., Manfredi C., Sorscher E., Mainou B., Lobby J.L., Kohlmeier J.E., Lowen A.C., Shi P.Y., Menachery V.D., Anderson L.J., Grakoui A., Bosinger S.E., Suthar M.S. (2020) Type I and type III interferons restrict SARS-CoV-2 infection of human airway epithelial cultures. J. Virol. 94(19), e00985-20.
  43. Sohn S.Y., Hearing J., Mugavero J., Kirillov V., Gorbunova E., Helminiak L., Mishra S., Mackow E., Hearing P., Reich N.C., Kim H.K. (2021) Interferon-lambda intranasal protection and differential sex pathology in a murine model of SARS-CoV-2 infection. mBio. 12(6), e0275621.
  44. Dijkman R., Verma A.K., Selvaraj M., Ghimire R., Gad H.H., Hartmann R., More S., Perlman S., Thiel V., Channappanavar R. (2022) Effective interferon lambda treatment regimen to control lethal MERS-CoV infection in mice. J. Virol. 96(11), e0036422. https://doi.org/10.1128/jvi.00364-22
  45. Stanifer M.L., Kee C., Cortese M., Zumaran C.M., Triana S., Mukenhirn M., Kraeusslich H.G., Alexandrov T., Bartenschlager R., Boulant S. (2020) Critical role of type III interferon in controlling SARS-CoV-2 infection in human intestinal epithelial cells. Cell Rep. 32(1), 107863.
  46. Dinnon K.H., Leist S.R., Schäfer A., Edwards C.E., Martinez D.R., Montgomery S.A., West A., Yount B.L., Hou Y.J., Adams L.E., Gully K.L., Brown A.J., Huang E., Bryant M.D., Choong I.C., Glenn J.S., Gralinski L.E., Sheahan T.P., Baric R.S. (2020) A mouse-adapted SARS-CoV-2 model for the evaluation of COVID-19 medical countermeasures. bioRxiv. 2020.05.06.081497. https://doi.org/10.1101/2020.05.06.081497
  47. Chong Z., Karl C.E., Halfmann P.J., Kawaoka Y., Winkler E.S., Yu J., Diamond M.S. (2022) Nasally-delivered interferon-λ protects mice against upper and lower respiratory tract infection of SARS-CoV-2 variants including Omicron. bioRxiv. 2022.01.21.477296. https://doi.org/10.1101/2022.01.21.477296
  48. Yadav D., Dewangan H.K. (2021) PEGYLATION: an important approach for novel drug delivery system. J. Biomater. Sci. Polym. Ed. 32(2), 266–280.
  49. Chan H.L.Y., Ahn S.H., Chang T.T., Peng C.Y., Wong D., Coffin C.S., Lim S.G., Chen P.J., Janssen H.L.A., Marcellin P., Serfaty L., Zeuzem S., Cohen D., Critelli L., Xu D., Wind-Rotolo M., Cooney E. (2016) Peginterferon lambda for the treatment of HBeAg-positive chronic hepatitis B: a randomized phase 2b study (LIR-A-B). J. Hepatol. 64(5), 1011–1019.
  50. Мадонов П.Г., Ершов К.И., Дубровин А.В., Заполоцкий Е.Н., Мирошников П.Н., Шилова, М.А. Киншт Д.Н. (2013) Электронно-лучевая модификация препаратов белковой природы для улучшения их фармакологических свойств. Медицина и образование в Сибири. 4, 83.
  51. Артамонов А.В., Бекарев А.А., Дыгай А.М., Жданов В.В., Киншт Д.Н., Мадонов П.Г., Шерстобоев Е.Ю. (2019) Пегилированный интерферон лямбда, обладающий высокой биодоступностью при пероральном применении, и способ его получения. Патент No. RU2678332C1, опубл. 2019.01.28.
  52. Мадонов П.Г., Святченко В.А., Легостаев С.С., Кихтенко Н.А., Котлярова А.А., Олейник Л.А., Байкалов Г.И., Удут В.В. (2021) Противовирусная активность в отношении SARS-CoV-2 фармацевтической субстанции на основе иммобилизированного рекомбинантного человеческого интерферона лямбда-1. Экспериментальная и клиническая фармакология. 84(7), 15‒20.
  53. Kubetzko S., Sarkar C.A., Plückthun A. (2005) Protein PEGylation decreases observed target association rates via a dual blocking mechanism. Mol. Pharmacol. 68(5), 1439–1454.
  54. Grace M.J., Lee S., Bradshaw S., Chapman J., Spond J., Cox S., Delorenzo M., Brassard D., Wylie D., Cannon-Carlson S., Cullen C., Indelicato S., Voloch M., Bordens D. (2005) Site of pegylation and polyethylene glycol molecule size attenuate interferon-alpha antiviral and antiproliferative activities through the JAK/STAT signaling pathway. J. Biol. Chem. 280(8), 6327–6336.
  55. Dinnon K.H., Leist S.R., Schäfer A., Edwards C.E., Martinez D.R., Montgomery S.A., West A., Yount B.L. Jr., Hou Y.J., Adams L.E., Gully K.L., Brown A.J., Huang E., Bryant M.D., Choong I.C., Glenn J.S., Gralinski L.E., Sheahan T.P., Baric R.S. (2020) A mouse-adapted model of SARS-CoV-2 to test COVID-19 countermeasures. Nature. 586(7830), 560–566.
  56. Feld J.J., Kandel C., Biondi M.J., Kozak R.A., Zahoor M.A., Lemieux C., Borgia S.M., Boggild A.K., Powis J., McCready J., Tan D.H.S., Chan T., Coburn B., Kumar D., Humar A., Chan A., O’Neil B., Noureldin S., Booth J., Hong R., Smookler D., Aleyadeh W., Patel A., Barber B., Casey J., Hiebert R., Mistry H., Choong I., Hislop C., Santer D.M., Lorne Tyrrell D., Glenn J.S., Gehring A.J., Janssen H.L.A., Hansen B.E. (2021) Peginterferon lambda for the treatment of outpatients with COVID-19: a phase 2, placebo-controlled randomised trial. Lancet Respir. Med. 9(5), 498–510.
  57. Jagannathan P., Andrews J.R., Bonilla H., Hedlin H., Jacobson K.B., Balasubramanian V., Purington N., Kamble S., de Vries C.R., Quintero O., Feng K., Ley C., Winslow D., Newberry J., Edwards K., Hislop C., Choong I., Maldonado Y., Glenn J., Bhatt A., Blish C., Wang T., Khosla C., Pinsky B.A., Desai M., Parsonnet J., Singh U. (2021) Peginterferon lambda-1α for treatment of outpatients with uncomplicated COVID-19: a randomized placebo-controlled trial. Nat. Commun. 12(1), 1967.

补充文件

附件文件
动作
1. JATS XML
2.

下载 (212KB)

版权所有 © Л.А. Олейник, П.Г. Мадонов, М.Б. Пыхтина, 2023

##common.cookie##