A Comprehensive Virology Platform

From in vitro assays setup to clinical trial support

WuXi Biology provides a comprehensive infectious disease platform with integrated drug discovery services from assay setup to clinical trial support. The outstanding infrastructure and instrumentation allow us to conduct high quality researches both in vitro and in vivo for our clients. Our Infectious Disease team provides world class services to accelerate your drug discovery process from target validation to PCC nomination.

The outstanding infrastructure and instrumentation allow us to conduct high quality researches both in vitro and in vivo for our clients.

  • BSL-2 facilities (>3,500 ft2), antiviral & antibacterial
  • ABSL-2 facilities (~3,000 ft2, 6 animal rooms, holding capacity of 5,000 rodents, ALAAAC accredited), antiviral & antibacterial
  • State-of-art instrumentation (e.g. COBAS system, POD810, Luminex, FACS, etc.)

Antiviral Services

In Vitro Research Platforms

  • Antiviral services: Cell-based and biochemical assays for HBV, RSV, influenza, HPIV, HIV, HSV, HCMV, ZIKA, HRV, EV71, CV and HCV for compound screening and profiling, resistance characterization, HTS and MOA studies
  • Support to clinical trials: Genotyping, VL determination, sequencing and phenotyping for HCV and HBV clinical trials; genotyping for RSV clinical trials

In Vivo Models

  • HDI, AAV/HBV and humanized mouse models for HBV, mouse and cotton rat pulmonary infection models for RSV, mouse lethal model for influenza virus, mouse lethal model for HSV and EV71, mouse xenograft model for HCMV

Hepatitis B Virus (HBV)

  • Compound screening
    • 2.15, DE19 and DES19 cell lines with qPCR, RT-qPCR, Southern blot, Northern blot, Western blot, ELISA and IF
    • Reporter cell lines (hTLR reporter, THP1-Blue™ ISG, TNF-Induced NF-κB-luciferase cell, etc.)
    • Biochemistry: capsid assembly quenching assay
  • Compound profiling: nuc and CpAM-resistance constructs, genotypes (A to J) and clinical strains, drug combination, serum shift, etc.
  • Ex vivo primary human hepatocytes (PHH) infectious system
  • In vivo models: HDI, AAV/HBV and humanized liver mouse models, endpoints with viral DNA, RNA and proteins in plasma and liver, and liver enzymes
  • HBV related immunological assays: cytokines, IFN/ISG and other immune markers (ELISA, Luminex, RT-qPCR, IF, IHC and Western blot), immune cell analysis (FACS, ICS and ELISPOT)
  • Support of clinical trials: VL, genotyping, sequencing, phenotyping, cytokines, pgRNA, HBcrAg
  • MOA studies: CpAM and customer tailored MOA studies

Respiratory Syncytial Virus (RSV)

  • Compound screening: RSV A and B lab and clinical strains with CPE, ELISA, neutralization and plaque reduction assays
  • Compound profiling: drug resistance, genotypic spectrum and drug combination
  • In vivo model: mouse or cotton rat pulmonary infection models with VL plaque assay
  • Support of clinical trials: VL, genotyping
  • MOA: F protein-mediated cell fusion

Influenza Virus (IFV)

  • Compound screening/profiling
    • A mini panel of IFV A H1N1 and H3N2, and IFV B strains with CPE, plaque and RT-qPCR
    • Highly pathogenic avian influenza H5N1 and H7N9 strains
    • Drug resistance, drug combination
  • In vivo model: mouse pulmonary infection with mortality and VL titration
  • Biochemistry: neuraminidase, hemagglutinin
  • Viral protein and replication complex purification from infected hen eggs

Human Parainfluenza Virus (HPIV)

  • HPIV-3 CPE assay

Human Immunodeficiency Virus (HIV)

  • HIV CPE assay in a subcontract lab
  • Viral enzymes

Herpes Simplex Virus (HSV)

  • Compound screening/profiling: HSV-1 and HSV-2, CPE and reporter assays
  • In vivo model: mouse lethal and ocular latent infection/activation models
  • Ex vivo model: isolation and cultivation of latently infected ganglia neurons

Human Cytomegalovirus (HCMV)

  • Compound screening: CPE and reporter assays
  • In vivo model: mouse xenograft model with VL titration

Hepatitis C Virus (HCV)

  • Compound screening: stable and transient replicons, and HCVcc with luciferase reporter and RT-qPCR
  • Compound profiling: drug resistance, genotypic spectrum, drug combination and serum shift
  • Support to clinical trials: VL, genotyping and phenotyping
  • Biochemistry: viral enzymes

Picornaviruses

  • Human rhinovirus (HRV): mini panel of HRV strains, CPE assay
  • Enterovirus 71 (EV71, hand-foot-mouth disease): CPE, mouse lethal and VL RT-qPCR model
  • Coxsackie virus (CV): A16 and B3, CPE assay

Zika Virus

  • Compound screening: CPE and plaque reduction assay
  • In vivo model: mouse lethal model with VL RT-qPCR

HBV Platform

Chronic hepatitis B (CHB) is a severe public health burden and an unmet medical need. Current standard therapies, interferon-α and nucleot(s)ides, cannot eliminate HBV. Recently, various novel targets and approaches are being explored towards the cure of CHB.  The Biology HBV team at WuXi AppTec, led by a group of experienced scientists with in-depth knowledge in anti-HBV drug discovery, has established and been providing an open access and full-range integrated HBV platform to our clients, including biochemical and cell-based assays, ex vivo PHH systems, animal models and clinical virology assays. The WuXi HBV team is your ideal partner for discovery and development of novel anti-HBV agents.

Services

A broad assay platform for the discovery of agents for the treatment of chronic HBV infection. Services for assay establishment and validation, compound screening and characterization, and support of preclinical studies and clinical trials.

In Vitro Assays

  • HBV stable cell lines : HepG2.2.15, DE19 and DES19
    •     HBV DNA, cccDNA (qPCR, dot blot, Southern blot)
    •     HBV antigens (ELISA, IHC, Western blot)
    •     HBV RNAs (Northern blot, RT-qPCR)
    •     Encapsidated RNA and DNA
    •     Capsid content
  • HBV DNA constructs with transient transfection assay
  • Clinical isolates/genotype A to J (~5 strains for each genotype)
  • Nucleot(s)ide and capsid inhibitor resistant mutants
  • Phenotyping with shuttle vectors and mutant constructs
    •     Fitness
    •     Drug sensitivity
  • HepG2-NTCP cell/HBV infectious system
  • Reporter cell lines (hTLR, THP1-Blue ISG, TNF-induced NF-κB-luciferase, and IFN-α/β induction SEAP)
  • Production of HBV from HBV stable cell lines
  • Recombinant core protein expression and purification, and capsid quenching assay
  • MOA studies

Clinical Virology (CAP lab)

  • Viral load (Cobas)
  • Sequencing: Pol, core, full-length sequencing, sanger (clone and population), deep sequencing
  • Genotyping by INNO-LiPA
  • Phenotyping
  • HBV emerging markers: serum HBV RNA, HBcrAg

PK/PD Study and HBV Animal Model Related Immunology Assays

  • Cytokines by ELISA, Luminex and MSD
  • IFN and ISG mRNA by ELISA and RT-qPCR
  • Immune markers by IHC, IF and Western blot
  • Splenocytes, lymphocytes from organs and PBMC by FACS, ICS and ELISPOT 

Animal Models

  • Hydrodynamic injection (HDI) mouse model
  • AAV/HBV mouse model
  • Humanized FRG mouse model
  • WHV/woodchuck model
Activity of ETV in AAV/HBV Mice

Ex Vivo Primary Human Hepatocytes (PHH)

  • Fresh isolated and cryopreserved PHH
  • In vitro HBV infection
  • In vivo HBV infection

Virology Assays Supporting Human Clinical Trials

Clinical Sample Testing

  • HCV
  • HBV
  • RSV

Automated Sample Preparation, Amplification and Quantitation

  • HCV RNA viral load
  • HBV DNA viral load

Genotyping

  • Taqman SNP and CNV assay
  • Sanger sequencing
  • SNPshot
  • MSI

Gene Expression Studies

  • Fresh tissues
  • Whole blood
  • FFPE