Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Human Cytomegalovirus Essential Tegument Protein pp150 is Amenable to Targeting by Sequence Specific Peptides and ELP-conjugates

Version 1 : Received: 31 August 2021 / Approved: 2 September 2021 / Online: 2 September 2021 (14:42:31 CEST)

A peer-reviewed article of this Preprint also exists.

Mitra, D.; Hasan, M.H.; Bates, J.T.; Bidwell, G.L., III; Tandon, R. Tegument Protein pp150 Sequence-Specific Peptide Blocks Cytomegalovirus Infection. Viruses 2021, 13, 2277. Mitra, D.; Hasan, M.H.; Bates, J.T.; Bidwell, G.L., III; Tandon, R. Tegument Protein pp150 Sequence-Specific Peptide Blocks Cytomegalovirus Infection. Viruses 2021, 13, 2277.

Abstract

Human cytomegalovirus (HCMV) tegument protein pp150 is essential for the completion of final steps in virion maturation. Earlier studies indicated that three pp150nt (N terminal one-third of pp150) conformers cluster on each triplex (Tri1, Tri2A and Tri2B) and extend towards small capsid proteins atop nearby major capsid proteins forming a net-like layer of tegument densities that enmesh and stabilize HCMV capsids. Based on this atomic detail, we designed several peptides targeting pp150nt. Our data show significant reduction in virus growth upon treatment with one of these peptides (pep-CR2) with an IC50 of 1.33 μM. Based on 3D modeling, pep-CR2 specifically interferes with the pp150-capsid binding interface. Cells pre-treated with pep-CR2 and infected with HCMV sequester pp150 in the nucleus indicating a mechanistic disruption of pp150 loading onto capsids and subsequent nuclear egress. To enhance the in-vivo inhibitory potential and bioavailability of pep-CR2, we conjugated it with a carrier molecule (elastin like polypeptide (ELP)). The ELP-pep-CR2 conjugate was expressed in E.coli and purified. Upon treatment with ELP-pep-CR2, HCMV showed significant titer reductions with no significant impact on cell viability. These results indicate that CR2 of pp150 is amenable to targeting by a peptide inhibitor and can be developed into an effective antiviral.

Keywords

CMV; herpesviruses; peptide therapy; tegument; nuclear egress

Subject

Biology and Life Sciences, Virology

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our Diversity statement.

Leave a public comment
Send a private comment to the author(s)
* All users must log in before leaving a comment
Views 0
Downloads 0
Comments 0
Metrics 0


×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.