title: Characterization of the inhibitory effect of an extract of Prunella vulgaris on Ebola virus glycoprotein (GP)-mediated virus entry and infection.
abstract: Currently, no approved antiviral therapeutic is available for treatment or prevention of Ebola virus (EBOV) infection. In this study, we characterized an EBOV-glycoprotein (GP) pseudotyped HIV-1-based vector system in different cell cultures, including human umbilical vein endothelial cells (HUVECs) and human macrophages, for the screening of anti-EBOV-GP agent(s). Based on this system, we demonstrated that an aqueous extract (CHPV) from the Chinese herb Prunella vulgaris displayed a potent inhibitory effect on EBOV-GP pseudotyped virus (EBOV-GP-V)-mediated infection in various cell lines, including HUVEC and macrophage. In addition, our results indicated that CHPV was able to block an eGFP-expressing Zaire ebola virus (eGFP-ZEBOV) infection in VeroE6 cells. The anti-EBOV activity of CHPV was exhibited in a dose-dependent manner. At a 12.5 μg/ml concentration, the CHPV showed a greater than 80% inhibition of EBOV-GP-V and eGFP-EBOV infections. Likewise, our studies suggested that the inhibitory effect of CHPV occurred by binding directly to EBOV-GP-Vs and blocking the early viral events. Interestingly, our results have shown that CHPV was able to enhance the anti-EBOV activity of the monoclonal antibody MAb 2G4 against EBOV-GP. Overall, this study provides evidence that CHPV has anti-EBOV activity and may be developed as a novel antiviral approach against EBOV infection.
authors.affiliation: Laboratory of Molecular Human Retrovirology, Department of Medical Microbiology, Faculty of Medicine, University of Manitoba, Canada.
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Laboratory of Molecular Human Retrovirology, Department of Medical Microbiology, Faculty of Medicine, University of Manitoba, Canada; Department of Microbiology, School of Basic Medical Sciences, Central South University, Changsha, Hunan, 410078, PR China.
authors.forename: Zhujun
authors.initials: Z
authors.lastname: Ao
authors.affiliation: Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Canada.
authors.forename: Alexander
authors.initials: A
authors.lastname: Bello
authors.affiliation: Laboratory of Molecular Human Retrovirology, Department of Medical Microbiology, Faculty of Medicine, University of Manitoba, Canada.
authors.forename: Xiaozhuo
authors.initials: X
authors.lastname: Ran
authors.affiliation: Department of Microbiology, School of Basic Medical Sciences, Central South University, Changsha, Hunan, 410078, PR China.
authors.forename: Shuiping
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Biochemistry and Medical Genetics, University of Manitoba, Canada.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Wigle
authors.affiliation: Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Canada.
authors.forename: Gary
authors.initials: G
authors.lastname: Kobinger
authors.affiliation: Laboratory of Molecular Human Retrovirology, Department of Medical Microbiology, Faculty of Medicine, University of Manitoba, Canada; Department of Microbiology, School of Basic Medical Sciences, Central South University, Changsha, Hunan, 410078, PR China. Electronic address: xiao-jian.yao@umanitoba.ca.
authors.forename: Xiaojian
authors.initials: X
authors.lastname: Yao
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D004353:Drug Evaluation, Preclinical; D004357:Drug Synergism; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology; D029043:Ebolavirus / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D057809:HEK293 Cells; D015497:HIV-1 / Q000235:genetics; D006367:HeLa Cells; D019142:Hemorrhagic Fever, Ebola / Q000517:prevention & control / Q000821:virology; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000821:virology; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000821:virology; D051379:Mice; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D031347:Prunella / Q000737:chemistry*; D014709:Vero Cells; D014760:Viral Fusion Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D053586:Virus Internalization / Q000187:drug effects*
chemical_list: D000911:Antibodies, Monoclonal; D000998:Antiviral Agents; D004365:Drugs, Chinese Herbal; D010936:Plant Extracts; D014760:Viral Fusion Proteins
keywords: Chinese herb Prunella vulgaris; EBOV-GP pseudovirions; Ebola virus (EBOV); Glycoprotein (GP); Monoclonal antibody MAb