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Updated: Jun 27, 2025
Engineering Antiviral Agents via Surface Plasmon Resonance
Published on: June 14, 2022
An Elastin-like Polypeptide-fusion peptide targeting capsid-tegument interface as an antiviral against
Komal Beeton1, Dipanwita Mitra1, Adesanya A Akinleye2
1Department of Cell and Molecular Biology, Center for Immunology and Microbial Research, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS, 39216, USA.
Abstract:
The tegument protein pp150 of Human Cytomegalovirus (HCMV) is known to be essential for the final stages of virus maturation and mediates its functions by interacting with capsid proteins. Our laboratory has previously identified the critical regions in pp150 important for pp150-capsid interactions and designed peptides similar in sequence to these regions, with a goal to competitively inhibit capsid maturation. Treatment with a specific peptide (PepCR2 or P10) targeted to pp150 conserved region 2 led to a significant reduction in murine CMV (MCMV) growth in cell culture, paving the way for in vivo testing in a mouse model of CMV infection. However, the general pharmacokinetic parameters of peptides, including rapid degradation and limited tissue and cell membrane permeability, pose a challenge to their successful use in vivo. Therefore, we designed a biopolymer-stabilized elastin-like polypeptide (ELP) fusion construct (ELP-P10) to enhance the bioavailability of P10. Antiviral efficacy and cytotoxic effects of ELP-P10 were studied in cell culture, and pharmacokinetics, biodistribution, and antiviral efficacy were studied in a mouse model of CMV infection. ELP-P10 maintained significant antiviral activity in cell culture, and this conjugation significantly enhanced P10 bioavailability in mouse tissues. The fluorescently labeled ELP-P10 accumulated to higher levels in mouse liver and kidneys as compared to the unconjugated P10. Moreover, viral titers from vital organs of MCMV-infected mice indicated a significant reduction of virus load upon ELP-P10 treatment. Therefore, ELP-P10 has the potential to be developed into an effective antiviral against CMV infection.
Insights
A novel peptide (P10) targeting Human Cytomegalovirus (HCMV) maturation was fused with elastin-like polypeptide (ELP) to create ELP-P10. This fusion enhanced peptide bioavailability and significantly reduced viral load in a mouse model of HCMV infection.
Area of Science:
- Virology
- Biotechnology
- Pharmacology
Background:
- Human Cytomegalovirus (HCMV) tegument protein pp150 is crucial for viral maturation.
- Peptides targeting pp150-capsid interactions can inhibit viral growth.
- Peptide pharmacokinetic limitations hinder in vivo antiviral development.
Purpose of the Study:
- To enhance the bioavailability and efficacy of an antiviral peptide (P10) targeting HCMV.
- To evaluate the pharmacokinetic and antiviral properties of an elastin-like polypeptide (ELP)-P10 fusion construct in vivo.
Main Methods:
- Designed and constructed an ELP-P10 fusion protein.
- Assessed antiviral activity and cytotoxicity of ELP-P10 in cell culture.
- Investigated pharmacokinetics, biodistribution, and antiviral efficacy in a murine model of CMV infection.
Main Results:
- ELP-P10 demonstrated significant antiviral activity in cell culture.
- Conjugation to ELP enhanced P10 bioavailability and tissue accumulation (liver, kidneys).
- ELP-P10 treatment significantly reduced viral titers in vital organs of infected mice.
Conclusions:
- ELP-P10 fusion construct effectively enhances peptide bioavailability and antiviral efficacy against CMV.
- ELP-P10 shows potential as a therapeutic agent for CMV infections.
