At CD BioSciences, we specialize in transforming early screening hits into validated, structurally optimized, and biologically characterized lead compounds specifically targeting human herpesviruses (HHVs). Our Hit-to-Lead (H2L) Generation Solutions are built upon a robust understanding of the complex biology of alpha-, beta-, and gamma-herpesviruses, with specialized capabilities in viral replication, latency, reactivation, and host-pathogen interaction.
Whether you're pursuing novel targets such as viral helicases, proteases, or latency-associated proteins like LANA, or repurposing broad-spectrum antivirals with anti-HHV activity, CD BioSciences offers integrated preclinical H2L services tailored to HHV biology and druggability.
Our HHV-Focused Hit-to-Lead Workflow
We provide a structured yet flexible workflow, optimized for HHV-specific antiviral drug discovery:
Hit Prioritization & Characterization
- Mechanism-based triage: We prioritize hits based on relevance to HHV targets (e.g., viral polymerases, immediate-early genes, tegument proteins).
- Assay reproducibility: All hits undergo retesting in orthogonal cell-based assays, including plaque reduction, cytopathic effect (CPE), and HHV-specific reporter systems.
- Cytotoxicity profiling: Evaluation of CC50 and selectivity index (SI) in host-relevant cell lines (e.g., Vero, HEK293, BCBL-1).
Structure-Activity Relationship (SAR) Exploration
- Medicinal chemistry design: SAR hypotheses are informed by the structure and physicochemical properties of prioritized hits.
- Analog library synthesis: Rapid synthesis and evaluation of analogs with modified scaffolds, substitutions, or linker optimizations.
- Activity refinement: Continuous in vitro evaluation against HHV strains (e.g., HSV-1, HSV-2, HCMV, EBV, KSHV) to monitor potency improvements.
Mechanism of Action (MoA) Elucidation
- Time-of-addition studies: To identify early vs. late viral lifecycle intervention points.
- Resistance profiling: Selection of resistant HHV strains under drug pressure, followed by sequencing of viral genes.
- Target validation: Combined use of genetic knockouts, overexpression, or CRISPR interference with compound treatment.
Lead Compound Selection Criteria
- Potency & selectivity: IC50 < 1 μM and SI > 100 preferred for nomination.
- Drug-likeness: Compliance with Lipinski's Rule of Five, favorable logP, PSA, and molecular weight.
- ADME screening: In vitro metabolic stability (liver microsomes), permeability (Caco-2), plasma protein binding, and solubility profiling.
Key Advantages of CD BioSciences' HHV H2L Services
Deep HHV Expertise
We maintain a virus-specific focus across all herpesvirus subfamilies—offering specialized knowledge in latency-associated gene expression (e.g., LANA in KSHV, EBNA1 in EBV), strain-specific tropism, and immune evasion.
Proprietary Tools & Assays
- HHV reporter viruses: For rapid antiviral screening.
- Latency reactivation assays: To test for efficacy in latent or reactivating virus contexts.
- Custom HHV cell models: Including primary neuronal and B cell latency models.
Seamless Integration with Upstream & Downstream Services
Our Hit-to-Lead generation is fully embedded within a larger antiviral discovery pipeline:
- Upstream: Hit identification via high-throughput screening or in silico docking.
- Downstream: Preclinical candidate nomination, IND-enabling studies, and PK/PD modeling.
Accelerated Timelines
With internal chemistry, virology, and assay teams, we rapidly iterate SAR cycles and deliver qualified lead compounds with defined MoA and pre-IND data packages.
Application Areas
Our HHV-specific hit-to-lead services have been applied in the discovery of antivirals targeting:
- Herpes Simplex Viruses (HSV-1/2): Viral helicase-primase inhibitors, entry blockers, latency reactivators.
- Varicella-Zoster Virus (VZV): DNA polymerase and capsid assembly inhibitors.
- Human Cytomegalovirus (HCMV): UL97 kinase and terminase complex inhibitors.
- Epstein-Barr Virus (EBV): LMP1/EBNA1 disruptors, latency reversing agents.
- Kaposi's Sarcoma-associated Herpesvirus (KSHV): LANA-targeted small molecules, K-Rta activators.
Collaborative Project Models
We offer flexible business and collaboration models:
- Fee-for-Service (FFS): Full execution of your hit-to-lead campaign with regular updates.
- FTE-based: Embedded scientist model for high-volume iterative SAR work.
- Milestone-based: Shared-risk models tied to lead optimization goals.
Typical Deliverables
By the end of a hit-to-lead project, you will receive:
- Prioritized lead series with SAR documentation.
- Confirmed MoA and antiviral profiling data.
- Drug-likeness and early ADME characterization.
- Recommendations for lead optimization and IND strategy.
Why Choose CD BioSciences?
- HHV specialization: We are the only platform with exclusive focus on HHV biology and preclinical drug development.
- Multidisciplinary integration: In-house medicinal chemistry, virology, molecular biology, and bioinformatics expertise.
- Tailored solutions: Custom design of screening and SAR strategies for your target class or indication.
- Regulatory awareness: We generate data packages aligned with preclinical requirements for US and EU regulatory filings.
Contact us to initiate your HHV-focused hit-to-lead project. Whether you are screening broad antiviral libraries or fine-tuning leads against latent reservoirs, CD BioSciences is your expert partner in HHV drug discovery.
References
- De Clercq E, Li G. Approved Antiviral Drugs over the Past 50 Years. Clin Microbiol Rev. 2016;29(3):695–747. doi:10.1128/CMR.00102-15
- Prichard MN, Kern ER. The search for new therapies for human cytomegalovirus infections. Virus Res. 2011;157(2):212–221.
- Wyles DL, Marcellin P, et al. Challenges in Drug Development for Latent Viral Infections. Nat Rev Drug Discov. 2020;19(12):878–900.
- Liu Y, et al. Identification of a Small-Molecule Inhibitor Targeting Kaposi's Sarcoma-Associated Herpesvirus LANA. J Virol. 2022;96(4):e0176121.
- Andrei G, Snoeck R. Advances in the treatment of alpha-herpesvirus infections. Curr Opin Infect Dis. 2013;26(3):231–239.