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Infectious Disease

Client recognitions:

  • Proven track record

    • 13 (integrated) medicinal chemistry programs, leading to 3 PCC nominations (2 FIH)
    • FTE- and FFS-projects for >20 pharmaceuticals, biotechs, and non-profit organizations
    • Significant increase in client-tailored projects with specific needs
    • Significant increase in client co-sponsored capability building
    • Expansion to new capabilities
  • High-level customer satisfaction

    • Multiple awards from clients for scientific and service excellence
    • Repeat business and expansion of collaborations
  • Flexible collaboration models

Upfront investment:

  • Seasoned management and well-experienced research teams

    • Senior management with experience in managing ID programs in US and Canada
    • Senior management with industrial R&D experiences
    • Experienced talents as group leaders
    • Internal training programs for all staff scientists (~80, 7.5% Ph.D., 60% M.S.,30% B.S.)
    • Highly stable & functional teams (with turn-over <5%)
  • Extensive capabilities

    • Broad pathogen spectra: viruses, bacteria, fungi
    • In vitro biology: compound screening, cell-based assays, molecular biology & genetics, biochemistry, enzymology, resistance studies, genomics…
    • Antiviral & antibacterial pharmacology: animal models in vivo efficacy studies
  • Outstanding infrastructure and instrumentation

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

Key Anti-Viral Services Capabilities

  • HCV:

    • Replicon and viral enzyme assays for SAR support
    • Resistance selection and mutant replicon development
    • Construction of inter-genotypic chimeras
    • Mutant and chimeric replicon fitness and drug-sensitivity analyses
    • Drug combination analysis
    • qRT-PCR analysis of viral load reduction and mutant analysis in 3-week treatment
    • Crystallography of viral proteins and complex
    • Clinical support
      - VLD using COBAS? AmpliPrep and TaqMan 48 systems
      - Clinical mutant phenotyping
    • Genotyping by NGS (in development)
  • HBV:

    • Drug screening using HBV producing cell lines and biochemical assay
      (qPCR, Southern blot, Dot blot, ELISA, Capsid assembly assay in vitro)
    • Mutant construction and compound profiling
      - Construction of drug-resistant mutants
      - Compound profiling against LAM-, ETV-, or LDT-resistant mutants by transfection (qPCR)

    • Drug combination assay
    • Clinical antiviral response analysis using the COBAS? system
    • Drug-resistant mutant cell lines
    • Mouse hydrodynamic injection model
    • Humanized FRG mouse model for HBV infection
    • HBV hydrodynamic injection mouse model:

      Humanized FRG mouse model for HBV infection

  • RSV:

    • Viral infection assays (CPE, plaque-reduction, Elisa, TaqMan)
    • Viral infection assays (CPE, plaque-reduction, Elisa, TaqMan)MOA studies (time of addition, cell fusion assay,syncytium formation assay, resistance selection…)
    • Mouse nasal infection model
    • Reverse genetics system and autonomous replication system (in development)
    • Cotton rat model (in development)

    RSV MOA studies:

  • Herpes antiviral service platform:

    • HSV (type 1 & 2), HCMV CPE-based screening assay
    • HSV, CMV reporter assay
    • HSV latency mouse model (Ganglion Explant Model)
    • Murine CMV acute & latent infection mouse model (in development)

    HSV latency mouse model

  • Influenza Virus:

    • Viral infection assays (CPE, plaque, TaqMan) for SAR support
    • CPE-based HTS (384w, Z-factor >0.8), Hit discovery and HTL
    • Hemolysis assay
    • Trypsin susceptibility assay
    • Mini influenza strain panel for anti-viral spectra analysis
    • Drug-resistant selection and seq analysis by NGS; MOA
    • Viral protein or replication complex purification from infected hen eggs
    • Mouse infection model for mortality and/or virus replication

    Validation of H1N1 (WSN) mouse model with Oseltamivir phosphate

  • Multi-virus Antiviral Panel

    • Picornaviridae, Herpesviridae, Orthomyxoviridae, Arteriviridae,Poxviridae, Flaviviridae, Retroviridae, Paramyxoviridae
    • CPE or reporter based assay (96w & 384w, Z-factor>0.6)
  • HIV:

    • Biochemical assays (IN and RT)
    • Pseudo type virus assay
    • HIV infectivity assay(in BSL-3 lab by subcontractor)
  • EV-71 (hand-foot-mouth disease):

    • 3C protease assay
    • Virus CPE and TaqMan assays
    • Mouse model (in development)
  • Dengue antiviral service platform(in development)

    • Dengue screening system: replicon with a reporter
    • Dengue enzyme assays
    • Mutagenesis cassette system

Key Anti-bacterial Capabilities

transferable to different bacterial pathogens

  • Microbiology

    • MIC as per CLSI (serum/protein shift), throughput = ~400 compound x strain / week,can increase with automation, HTS capability available
    • MBC, standard and simplified (coupled with MIC)
    • Spectrum (~10, Gram + & -, as per client request)
    • Time-kill curve
    • Post antibiotic effect (PAE)
    • Synergy/potentiation assay
  • Genetics & Genomics

    • Frequency of resistance (FOR)
    • Drug-induced resistant mutation, isolation & characterization
    • Genomic sequencing by NGS
  • Biochemistry

    • Quantitative MOA
    • Enzymatic assays
    • Macromolecular labeling
    • turnaround time = 1 week
    • throughput per week = ~20compounds, panel of ~15 strains
  • Pharmacology

    • Animal models of bacterial infection
    • In vivo efficacy
    • Deep-thigh model of S. aureus:
      • immuno-compromised host
      • in vivo efficacy of small molecules
      • turnaround time, ~1 week
      Systemic model of S. aureus:
      • immuno-competent or -compromised host
      • in vivo efficacy of small molecules & biologics
      • turnaround time, 1 – 2 week(s)
      Pulmonary model of P. aeruginosa:
      • immuno-competent or -compromised host
      • in vivo efficacy of small molecules
      • turnaround time, 1 week (acute infection)

Key High Throughput Screening Capabilities:

  • Assay development (GPCR, kinases, ion channel, etc...)

  • 753 plates of 384-w Echo-ready plates of diverse and unique WuXi compound collection screening

  • Client compound library screening (up to 1M) in 384-w format

  • 95 GPCR stable cell lines ready in FLIPR assay