loading page

Hesperetin blocks poxvirus replication by competitively inhibiting binding of the 5' cap of viral mRNA with eIF4E
  • +8
  • Naveen Kumar,
  • Assim Verma,
  • Ramesh Kumar Dedar,
  • Ram Kumar,
  • Yogesh Chander,
  • Himanshu Kamboj,
  • Rekha Verma,
  • Santosh Kumari,
  • Shalini Sharma,
  • Bhupendra N. Tripathi,
  • Sanjay Barua
Naveen Kumar
National Research Centre on Equines

Corresponding Author:naveen.kumar1@icar.gov.in

Author Profile
Assim Verma
National Research Centre on Equines
Author Profile
Ramesh Kumar Dedar
National Research Centre on Equines
Author Profile
Ram Kumar
National Research Centre on Equines
Author Profile
Yogesh Chander
National Research Centre on Equines
Author Profile
Himanshu Kamboj
National Research Centre on Equines
Author Profile
Rekha Verma
Pandit Bhagwat Dayal Sharma Post Graduate Institute of Medical Sciences Rohtak
Author Profile
Santosh Kumari
Guru Jambheshwar University of Science & Technology
Author Profile
Shalini Sharma
National Research Centre on Equines
Author Profile
Bhupendra N. Tripathi
National Research Centre on Equines
Author Profile
Sanjay Barua
National Research Centre on Equines
Author Profile

Abstract

In this study, hesperetin was shown to inhibit the replication of multiple poxviruses, including buffalopox virus (BPXV), vaccinia virus, and lumpy skin disease virus (LSDV). Hesperetin mainly suppressed viral protein synthesis without affecting other steps of the viral life cycle such as attachment, entry, and budding. In a chromatin immunoprecipitation (CHIP) assay, we further demonstrated that hesperetin-induced reduction in BPXV protein synthesis is due to disruption of the binding of the 5’ cap of viral mRNA with the cellular translation initiation factor eIF4E. The molecular docking and MD simulation studies, also confirmed binding of the hesperetin with the cap-binding pocket of eIF4E, in a similar conformation as m7GTP binds. In a BPXV egg infection model, hesperetin was shown to suppress the development of pock lesions on the chorioallantoic membrane, as well as the associated mortality of the chicken embryos. Most importantly, long-term culture of BPXV in the presence of hesperetin did not induce the generation of drug-resistant viral mutants. In conclusion, we for the first time demonstrated the antiviral activity of hesperetin against poxviruses, besides providing novel mechanistic insights into the antiviral action of hesperetin.
22 Sep 2023Submitted to Journal of Medical Virology
22 Sep 2023Submission Checks Completed
22 Sep 2023Assigned to Editor
22 Sep 2023Review(s) Completed, Editorial Evaluation Pending
10 Oct 2023Reviewer(s) Assigned
27 Oct 2023Editorial Decision: Revise Major
23 Feb 2024Review(s) Completed, Editorial Evaluation Pending
07 Mar 2024Editorial Decision: Revise Major
09 Mar 2024Submission Checks Completed
09 Mar 2024Assigned to Editor
09 Mar 2024Review(s) Completed, Editorial Evaluation Pending
11 Mar 2024Editorial Decision: Accept