Characterization of the inhibitory effect of an extract of Prunella vulgaris on Ebola virus glycoprotein (GP)-mediated virus entry and infection

Antiviral Research

Volumn 127, Issue , 2016, Pages 20-31

  Zhang, Xu ^a   Ao, Zhujun ^a,b   Bello, Alexander ^c   Ran, Xiaozhuo ^a   Liu, Shuiping ^b   Wigle, Jeffrey ^a   Kobinger, Gary ^c   Yao, Xiaojian ^a,b  

^a UNIVERSITY OF MANITOBA   (Canada)

^b CENTRAL SOUTH UNIVERSITY   (China)

^c PUBLIC HEALTH AGENCY OF CANADA   (Canada)

Author keywords

Chinese herb Prunella vulgaris; Ebola virus (EBOV); EBOV GP pseudovirions; Glycoprotein (GP); Monoclonal antibody MAb

Indexed keywords

PRUNELLA VULGARIS EXTRACT; VIRUS GLYCOPROTEIN; VIRUS VECTOR; ANTIVIRUS AGENT; HERBACEOUS AGENT; MONOCLONAL ANTIBODY; PLANT EXTRACT; VIRUS FUSION PROTEIN;

A549 CELL LINE; ANTIVIRAL ACTIVITY; ARTICLE; CELL CULTURE; CHINESE HERB; CYTOTOXICITY; DEMOCRATIC REPUBLIC CONGO; DOSE RESPONSE; DRUG PURIFICATION; DRUG SCREENING; DRUG SYNTHESIS; EBOLA HEMORRHAGIC FEVER; EBOLAVIRUS; EMBRYO; ENZYME LINKED IMMUNOSORBENT ASSAY; FEMALE; HEK293 CELL LINE; HELA CELL LINE; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS 1; MACROPHAGE; NONHUMAN; PRIORITY JOURNAL; PRUNELLA; PRUNELLA VULGARIS; UMBILICAL VEIN ENDOTHELIAL CELL; VIRUS ENTRY; ANIMAL; ANTAGONISTS AND INHIBITORS; CELL LINE; CHEMISTRY; DRUG EFFECTS; DRUG POTENTIATION; GENETICS; HEMORRHAGIC FEVER, EBOLA; METABOLISM; MOUSE; PHYSIOLOGY; PRECLINICAL STUDY; VERO CELL LINE; VIROLOGY;

ANIMALS; ANTIBODIES, MONOCLONAL; ANTIVIRAL AGENTS; CELL LINE; DRUG EVALUATION, PRECLINICAL; DRUG SYNERGISM; DRUGS, CHINESE HERBAL; EBOLAVIRUS; HEK293 CELLS; HELA CELLS; HEMORRHAGIC FEVER, EBOLA; HIV-1; HUMAN UMBILICAL VEIN ENDOTHELIAL CELLS; HUMANS; MACROPHAGES; MICE; PLANT EXTRACTS; PRUNELLA; VERO CELLS; VIRAL FUSION PROTEINS; VIRUS INTERNALIZATION;

EID: 84954535664     PISSN: 01663542     EISSN: 18729096     Source Type: Journal    
DOI: 10.1016/j.antiviral.2016.01.001     Document Type: Article

References (81)

1. S.C. Ahn, W.K. Oh, B.Y. Kim, D.O. Kang, M.S. Kim, G.Y. Heo, and J.S. Ahn Inhibitory effects of rosmarinic acid on Lck SH2 domain binding to a synthetic phosphopeptide Planta Med. 69 2003 642 646
2. I. Al-Bayati, M. Teleb, K. Lowder, and H.J. Salameh ZMapp: a new cocktail of monoclonal antibodies with much promise in containing the current Epidemic of ebola virus disease Med. Sci. Rev. 2 2015 32 34
3. Z. Ao, G. Huang, H. Yao, Z. Xu, M. Labine, A.W. Cochrane, and X. Yao Interaction of human immunodeficiency virus type 1 integrase with cellular nuclear import receptor importin 7 and its impact on viral replication J. Biol. Chem. 282 2007 13456 13467
4. Z. Ao, X. Wang, A.J. Bello, K. Danappa Jayappa, Z. Yu, K. Fowke, X. He, X. Chen, J. Li, G.P. Kobinger, and X. Yao Characterization of anti-HIV activity mediated by R88-Apobec3G mutant fusion proteins in CD4+ T cells, PBMCs and macrophages Hum. Gene Ther. 22 2011 1225 1237
5. J. Audet, G. Wong, H. Wang, G. Lu, G.F. Gao, G. Kobinger, and X. Qiu Molecular characterization of the monoclonal antibodies composing ZMAb: a protective cocktail against Ebola virus Sci. Rep. 4 2014
6. C. Barton, J.C. Kouokam, A.B. Lasnik, O. Foreman, A. Cambon, G. Brock, D.C. Montefiori, F. Vojdani, A.A. McCormick, and B.R. O'Keefe Activity of and effect of subcutaneous treatment with the broad-spectrum antiviral lectin griffithsin in two laboratory rodent models Antimicrob. Agents Chemother. 58 2014 120 127
7. A. Basu, B. Li, D.M. Mills, R.G. Panchal, S.C. Cardinale, M.M. Butler, N.P. Peet, H. Majgier-Baranowska, J.D. Williams, and I. Patel Identification of a small-molecule entry inhibitor for filoviruses J. Virol. 85 2011 3106 3119
8. M. Bray, and T.W. Geisbert Ebola virus: the role of macrophages and dendritic cells in the pathogenesis of Ebola hemorrhagic fever Int. J. Biochem. Cell Biol. 37 2005 1560 1566
9. M. Côté, J. Misasi, T. Ren, A. Bruchez, K. Lee, C.M. Filone, L. Hensley, Q. Li, D. Ory, and K. Chandran Small molecule inhibitors reveal Niemann-Pick C1 is essential for Ebola virus infection Nature 477 2011 344 348
10. J. Chang, T.K. Warren, X. Zhao, T. Gill, F. Guo, L. Wang, M.A. Comunale, Y. Du, D.S. Alonzi, and W. Yu Small molecule inhibitors of ER α-glucosidases are active against multiple hemorrhagic fever viruses Antivir. Res. 98 2013 432 440
11. R.S. Chang, L. Ding, C. Gai-Qing, P. Qi-Choa, Z. Ze-Lin, and K.M. Smith Dehydroandrographolide succinic acid monoester as an inhibitor against the human immunodeficiency virus Exp. Biol. Med. 197 1991 59 66
12. L.C. Chiu, W. Zhu, and V.E. Ooi A polysaccharide fraction from medicinal herb Prunella vulgaris downregulates the expression of herpes simplex virus antigen in Vero cells J. Ethnopharmacol. 93 2004 63 68
13. J.M. DiNapoli, L. Yang, S.K. Samal, B.R. Murphy, P.L. Collins, and A. Bukreyev Respiratory tract immunization of non-human primates with a Newcastle disease virus-vectored vaccine candidate against Ebola virus elicits a neutralizing antibody response Vaccine 29 2010 17 25
14. H.F. Dvorak, L.F. Brown, M. Detmar, and A.M. Dvorak Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis Am. J. pathology 146 1995 1029
15. H. Ebihara, S. Theriault, G. Neumann, J.B. Alimonti, J.B. Geisbert, L.E. Hensley, A. Groseth, S.M. Jones, T.W. Geisbert, Y. Kawaoka, and H. Feldmann 2007, in vitro and in vivo characterization of recombinant Ebola viruses expressing enhanced green fluorescent protein J. Infect. Dis. 196 2007 s313 S322
16. L.H. Elliott, M.P. Kiley, and J.B. McCormick Descriptive analysis of Ebola virus proteins Virology 147 1985 169 176
17. X. Fang, R.C.-C. Chang, W.-H. Yuen, and S.Y. Zee Immune modulatory effects of Prunella vulgaris L Int. J. Mol. Med. 15 2005 491 496
18. X. Fang, M.M.-S. Yu, W.-H. Yuen, S.Y. Zee, and R.C.-C. Chang Immune modulatory effects of Prunella vulgaris L. on monocytes/macrophages Int. J. Mol. Med. 16 2005 1109 1116
19. C. Fiore, M. Eisenhut, R. Krausse, E. Ragazzi, D. Pellati, D. Armanini, and J. Bielenberg Antiviral effects of Glycyrrhiza species Phytotherapy Res. 22 2008 141 148
20. G. Gehring, K. Rohrmann, N. Atenchong, E. Mittler, S. Becker, F. Dahlmann, S. Pöhlmann, F.W. Vondran, S. David, and M.P. Manns The clinically approved drugs amiodarone, dronedarone and verapamil inhibit filovirus cell entry J. Antimicrob. Chemother. 69 2014 2123 2131
21. S. HARADA THE BROAD ANTI-VIRAL AGENT GLYCYRRHIZIN DIRECTLY MODULATES THE FLUIDITY OF PLASMA MEMBRANE AND HIV-1 ENVELOPE BIOCHEM. J. 392 2005 191 199
22. H.A. Harrop, and C.C. Rider Heparin and its derivatives bind to HIV-1 recombinant envelope glycoproteins, rather than to recombinant HIV-1 receptor, CD4 Glycobiology 8 1998 131 137
23. K. Hayashi, T. Hayashi, and I. Kojima A natural sulfated polysaccharide, calcium spirulan, isolated from Spirulina platensis: in vitro and ex vivo evaluation of anti-herpes simplex virus and anti-human immunodeficiency virus activities AIDS Res. Hum. Retroviruses 12 1996 1463 1471
24. T. Hayashi Studies on evaluation of natural products for antiviral effects and their applications Yakugaku Zasshi J. Pharm. Soc. Jpn. 128 2008 61 79
25. T. Hayashi, K. Hayashi, M. Maeda, and I. Kojima Calcium spirulan, an inhibitor of enveloped virus replication, from a blue-green alga Spirulina platensis J. Nat. Prod. 59 1996 83 87
26. C.-c. Huang, M. Tang, M.-Y. Zhang, S. Majeed, E. Montabana, R.L. Stanfield, D.S. Dimitrov, B. Korber, J. Sodroski, and I.A. Wilson Structure of a V3-containing HIV-1 gp120 core Science 310 2005 1025 1028
27. T. Izumi, M. Hirata, K. Takahashi, and E. Kokufuta Complexation of papain with strong polyanions and enzymatic activities of the resulting complexes J. Macromol. Science - Pure Appl. Chem. 31 1994 39 51
28. K.D. Jayappa, Z. Ao, X. Wang, A.J. Mouland, S. Shekhar, X. Yang, and X. Yao Human immunodeficiency virus type 1 Employs the cellular Dynein Light chain 1 protein for Reverse transcription through interaction with its integrase protein J. Virol. JVI 2015 03347-03314
29. L.M. Johansen, J.M. Brannan, S.E. Delos, C.J. Shoemaker, A. Stossel, C. Lear, B.G. Hoffstrom, L.E. DeWald, K.L. Schornberg, and C. Scully FDA-approved selective estrogen receptor modulators inhibit Ebola virus infection Sci. Transl. Med. 5 2013 190ra179
30. L.-J. Kang, Y.-J. Choi, and S.-G. Lee Stimulation of TRAF6/TAK1 degradation and inhibition of JNK/AP-1 signalling by ginsenoside Rg3 attenuates hepatitis B virus replication Int. J. Biochem. Cell Biol. 45 2013 2612 2621
31. C.G. Kevil, D.K. Payne, E. Mire, and J.S. Alexander Vascular permeability factor/vascular endothelial cell growth factor-mediated permeability occurs through disorganization of endothelial junctional proteins J. Biol. Chem. 273 1998 15099 15103
32. G.P. Kobinger, D.J. Weiner, Q.-C. Yu, and J.M. Wilson Filovirus-pseudotyped lentiviral vector can efficiently and stably transduce airway epithelia in vivo Nat. Biotechnol. 19 2001 225 230
33. M.H. Lee, D.J. Seo, J.-H. Kang, S.H. Oh, and C. Choi Expression of antiviral cytokines in Crandell-Reese feline kidney cells pretreated with Korean red ginseng extract or ginsenosides Food Chem. Toxicol. 70 2014 19 25
34. B.D. Lenny Bernstein Ebola Test Drug's Supply 'exhausted' after Shipments to Africa 2014 U.S. company says Washington Post
35. P. Li, X. Hao, C. Zhao, Y. Chang, B. Wang, and H. Wu Study on the antiviral activities of ginsenoside-Rg3 and-Rb3 Chin. J. Gerontol. 21 2001 215 216
36. G. Lin, G. Simmons, S. Pöhlmann, F. Baribaud, H. Ni, G.J. Leslie, B.S. Haggarty, P. Bates, D. Weissman, and J.A. Hoxie Differential N-linked glycosylation of human immunodeficiency virus and Ebola virus envelope glycoproteins modulates interactions with DC-SIGN and DC-SIGNR J. Virol. 77 2003 1337 1346
37. S. Liu, S. Jiang, Z. Wu, L. Lv, J. Zhang, Z. Zhu, and S. Wu Identification of inhibitors of the HIV-1 gp41 six-helix bundle formation from extracts of Chinese medicinal herbs Prunella vulgaris and Rhizoma cibotte Life Sci. 71 2002 1779 1791
38. M. McCarthy US signs contract with ZMapp maker to accelerate development of the Ebola drug BMJ 349 2014 g5488
39. J. Misasi, and N.J. Sullivan Camouflage and misdirection: the full-on assault of Ebola virus disease Cell 159 2014 477 486
40. M. Moulard, H. Lortat-Jacob, I. Mondor, G. Roca, R. Wyatt, J. Sodroski, L. Zhao, W. Olson, P.D. Kwong, and Q.J. Sattentau Selective interactions of polyanions with basic surfaces on human immunodeficiency virus type 1 gp120 J. Virol. 74 2000 1948 1960
41. C.D. Murin, M.L. Fusco, Z.A. Bornholdt, X. Qiu, G.G. Olinger, L. Zeitlin, G.P. Kobinger, A.B. Ward, and E.O. Saphire Structures of protective antibodies reveal sites of vulnerability on Ebola virus Proc. Natl. Acad. Sci. 111 2014 17182 17187
42. C. Oh, J. Price, M.A. Brindley, M.P. Widrlechner, L. Qu, J.A. McCoy, P. Murphy, C. Hauck, and W. Maury Inhibition of HIV-1 infection by aqueous extracts of Prunella vulgaris L Virol. J. 8 2011 188
43. A. Patel, K. Tran, M. Gray, Y. Li, Z. Ao, X. Yao, D. Kobasa, and G.P. Kobinger Evaluation of conserved and variable influenza antigens for immunization against different isolates of H5N1 viruses Vaccine 27 2009 3083 3089
44. J. Pettitt, L. Zeitlin, D.H. Kim, C. Working, J.C. Johnson, O. Bohorov, B. Bratcher, E. Hiatt, S.D. Hume, and A.K. Johnson Therapeutic intervention of Ebola virus infection in rhesus macaques with the MB-003 monoclonal antibody cocktail Sci. Transl. Med. 5 2013 199ra113
45. J. Psotova, M. Kolář, J. Soušek, Z. Švagera, J. Vičar, and J. Ulrichová Biological activities of Prunella vulgaris extract Phytother. Res. 17 2003 1082 1087
46. X. Qiu, J.B. Alimonti, P.L. Melito, L. Fernando, U. Ströher, and S.M. Jones Characterization of Zaire ebolavirus glycoprotein-specific monoclonal antibodies Clin. Immunol. 141 2011 218 227
47. X. Qiu, J. Audet, G. Wong, S. Pillet, A. Bello, T. Cabral, J.E. Strong, F. Plummer, C.R. Corbett, and J.B. Alimonti Successful treatment of Ebola virus-infected cynomolgus macaques with monoclonal antibodies Sci. Transl. Med. 4 2012 138ra181
48. X. Qiu, L. Fernando, P.L. Melito, J. Audet, H. Feldmann, G. Kobinger, J.B. Alimonti, and S.M. Jones Ebola GP-specific monoclonal antibodies protect mice and guinea pigs from lethal Ebola virus infection PLoS Negl. Trop. Dis. 6 2012 e1575
49. X. Qiu, G. Wong, J. Audet, A. Bello, L. Fernando, J.B. Alimonti, H. Fausther-Bovendo, H. Wei, J. Aviles, and E. Hiatt Reversion of advanced Ebola virus disease in nonhuman primates with ZMapp Nature 514 2014 47 53
50. X. Qiu, G. Wong, L. Fernando, J. Audet, A. Bello, J. Strong, J.B. Alimonti, and G.P. Kobinger mAbs and Ad-vectored IFN-α therapy rescue Ebola-infected nonhuman primates when administered after the detection of viremia and symptoms Sci. Transl. Med. 5 2013 207ra143
51. S.Y. Ryu, M.-H. Oak, S.-K. Yoon, D.-I. Cho, G.-S. Yoo, T.-S. Kim, and K.-M. Kim Anti-allergic and anti-inflammatory triterpenes from the herb of Prunella vulgaris Planta Med. 66 2000 358 360
52. H. Sato, W. Goto, J.-i. Yamamura, M. Kurokawa, S. Kageyama, T. Takahara, A. Watanabe, and K. Shiraki Therapeutic basis of glycyrrhizin on chronic hepatitis B Antivir. Res. 30 1996 171 177
53. S. Seubsasana, C. Pientong, T. Ekalaksananan, S. Thongchai, and C. Aromdee A potential andrographolide analogue against the replication of herpes simplex virus type 1 in vero cells Med. Chem. 7 2011 237 244
54. T.-Y. Shin, Y.-K. Kim, and H.-M. Kim Inhibition of immediate-type allergic reactions by Prunella vulgaris in a murine model Immunopharmacol. Immunotoxicol. 23 2001 423 435
55. G. Simmons, J.D. Reeves, C.C. Grogan, L.H. Vandenberghe, F. Baribaud, J.C. Whitbeck, E. Burke, M.J. Buchmeier, E.J. Soilleux, and J.L. Riley DC-SIGN and DC-SIGNR bind ebola glycoproteins and enhance infection of macrophages and endothelial cells Virology 305 2003 115 123
56. G. Simmons, R.J. Wool-Lewis, F. Baribaud, R.C. Netter, and P. Bates Ebola virus glycoproteins induce global surface protein down-modulation and loss of cell adherence J. Virol. 76 2002 2518 2528
57. H.-X. Sun, F. Qin, and Y.-J. Pan In vitro and in vivo immunosuppressive activity of Spica prunellae ethanol extract on the immune responses in mice J. Ethnopharmacol. 101 2005 31 36
58. H.D. Tabba, R.S. Chang, and K.M. Smith Isolation, purification, and partial characterization of prunellin, an anti-HIV component from aqueous extracts of Prunella vulgaris Antivir. Res. 11 1989 263 273
59. A. Takada, K. Fujioka, M. Tsuiji, A. Morikawa, N. Higashi, H. Ebihara, D. Kobasa, H. Feldmann, T. Irimura, and Y. Kawaoka Human macrophage C-type lectin specific for galactose and N-acetylgalactosamine promotes filovirus entry J. Virol. 78 2004 2943 2947
60. A. Takada, C. Robison, H. Goto, A. Sanchez, K.G. Murti, M.A. Whitt, and Y. Kawaoka A system for functional analysis of Ebola virus glycoprotein Proc. Natl. Acad. Sci. 94 1997 14764 14769
61. M.R.S. Vincent, C.C. Colpitts, A.V. Ustinov, M. Muqadas, M.A. Joyce, N.L. Barsby, R.F. Epand, R.M. Epand, S.A. Khramyshev, and O.A. Valueva Rigid amphipathic fusion inhibitors, small molecule antiviral compounds against enveloped viruses Proc. Natl. Acad. Sci. 107 2010 17339 17344
62. R.R. Vives, A. Imberty, Q.J. Sattentau, and H. Lortat-Jacob Heparan sulfate targets the HIV-1 envelope glycoprotein gp120 coreceptor binding site J. Biol. Chem. 280 2005 21353 21357
63. V.E. Volchkov, S. Becker, V.A. Volchkova, V.A. Ternovoj, A.N. Kotov, S.V. Netesov, and H.-d. Klenk GP mRNA of ebola virus is Edited by the ebola virus polymerase and by T7 and Vaccinia virus polymerases 1 Virology 214 1995 421 430
64. V.E. Volchkov, H. Feldmann, V.A. Volchkova, and H.-D. Klenk Processing of the Ebola virus glycoprotein by the proprotein convertase furin Proc. Natl. Acad. Sci. 95 1998 5762 5767
65. V. Wahl-Jensen, S.K. Kurz, P.R. Hazelton, H.-J. Schnittler, U. Ströher, D.R. Burton, and H. Feldmann Role of Ebola virus secreted glycoproteins and virus-like particles in activation of human macrophages J. Virol. 79 2005 2413 2419
66. Z. Wen, B. Zhao, K. Song, X. Hu, W. Chen, D. Kong, J. Ge, and Z. Bu Recombinant lentogenic Newcastle disease virus expressing Ebola virus GP infects cells independently of exogenous trypsin and uses macropinocytosis as the major pathway for cell entry Virology J. 10 2013 331
67. J. Wilson, C. Bosio, and M. Hart Ebola virus: the search for vaccines and treatments Cell. Mol. Life Sci. CMLS 58 2001 1826 1841
68. M.C. Wolf, A.N. Freiberg, T. Zhang, Z. Akyol-Ataman, A. Grock, P.W. Hong, J. Li, N.F. Watson, A.Q. Fang, and H.C. Aguilar A broad-spectrum antiviral targeting entry of enveloped viruses Proc. Natl. Acad. Sci. 107 2010 3157 3162
69. J. Won, Y.G. Hur, E.M. Hur, S.H. Park, M. Kang, Y. Choi, C. Park, K.H. Lee, and Y. Yun Rosmarinic acid inhibits TCR-induced T cell activation and proliferation in an Lck-dependent manner Eur. J. Immunol. 33 2003 870 879
70. A.C. Wong, R.G. Sandesara, N. Mulherkar, S.P. Whelan, and K. Chandran A forward genetic strategy reveals destabilizing mutations in the Ebolavirus glycoprotein that alter its protease dependence during cell entry J. Virol. 84 2010 163 175
71. R.J. Wool-Lewis, and P. Bates Characterization of Ebola virus entry by using pseudotyped viruses: identification of receptor-deficient cell lines J. Virol. 72 1998 3155 3160
72. H.X. Xu, S.H. Lee, S.F. Lee, R.L. White, and J. Blay Isolation and characterization of an anti-HSV polysaccharide from Prunella vulgaris Antivir. Res. 44 1999 43 54
73. Z.-y. Yang, R. Delgado, L. Xu, R.F. Todd, E.G. Nabel, A. Sanchez, and G.J. Nabel Distinct cellular interactions of secreted and transmembrane Ebola virus glycoproteins Science 279 1998 1034 1037
74. Z.-y. Yang, H.J. Duckers, N.J. Sullivan, A. Sanchez, E.G. Nabel, and G.J. Nabel Identification of the Ebola virus glycoprotein as the main viral determinant of vascular cell cytotoxicity and injury Nat. Med. 6 2000 886 889
75. X.-J. Yao, A.J. Mouland, R.A. Subbramanian, J. Forget, N. Rougeau, D. Bergeron, and E.A. Cohen Vpr stimulates viral expression and induces cell killing in human immunodeficiency virus type 1-infected dividing Jurkat T cells J. Virol. 72 1998 4686 4693
76. X.-J. Yao, M.A. Wainberg, and M.A. Parniak Mechanism of inhibition of HIV-1 infection in Vitro by purified extract of Prunella vulgaris Virology 187 1992 56 62
77. A. Yonezawa, M. Cavrois, and W.C. Greene Studies of ebola virus glycoprotein-mediated entry and fusion by using pseudotyped human immunodeficiency virus type 1 virions: involvement of cytoskeletal proteins and enhancement by tumor necrosis factor alpha J. Virol. 79 2005 918 926
78. O. Yoshida, H. Nakashima, T. Yoshida, Y. Kaneko, I. Yamamoto, K. Matsuzaki, T. Uryu, and N. Yamamoto Sulfation of the immunomodulating polysaccharide lentinan: a novel strategy for antivirals to human immunodeficiency virus (HIV) Biochem. Pharmacol. 37 1988 2887 2891
79. Y. Zhang, P.P.-H. But, V.E.-C. Ooi, H.-X. Xu, G.D. Delaney, S.H. Lee, and S.F. Lee Chemical properties, mode of action, and in vivo anti-herpes activities of a lignin-carbohydrate complex from Prunella vulgaris Antivir. Res. 75 2007 242 249
80. Y. Zhang, D. Li, X. Jin, and Z. Huang Fighting Ebola with ZMapp: spotlight on plant-made antibody Sci. China Life Sci. 57 2014 987 988
81. M. Zheng Experimental study of 472 herbs with antiviral action against the herpes simplex virus Zhong Xi Yi Jie He Za Zhi 10 1990 39-41