In vitro inhibitory activity against HPV of the monoterpenoid zinc tetra-ascorbo-camphorate

Ralph Sydney Mboumba Bouassa,Bernard Gombert,Gabin Mwande-Maguene,Aurèle Mannarini,Laurent Bélec

doi:10.1016/j.heliyon.2021.e07232

Abstract

Zinc tetra-ascorbo-camphorate (or drug “C14”) is a synthetic monoterpenoid derivative that has potent anti-HIV-1 activity in vitro. In this study, we evaluated the in vitro antiviral properties of C14 against human papillomavirus (HPV). Inhibition assay of HPV-16-pseudovirus (PsVs) adsorption on COS-7 cells by C14 was used. C14 inhibited HPV-16-PsVs adsorption with IC50 ranging between 2.9 and 8.3 μM and therapeutic indexes between >410 to >3,300. Pretreatment of COS-7 cells with C14 before addition of HPV-16-PsV was associated with more potent anti-HPV activity than simultaneous deposition on COS-7 of HPV-16-PsV and C14, suggesting that C14 is more effective in preventing HPV attachment to target cells than post-HPV adsorption viral events. Overall, these in vitro studies suggest that the monoterpenoid zinc tetra-ascorbo-camphorate molecule may be suitable for further clinical evaluations as potential microbicide or therapeutic drug.

Highlights

Human papillomavirus (HPV) infection is the most common viral sexually transmitted infection worldwide and high risk-HPV (HR-HPV) genotypes, HPV-16 and HPV-18, are responsible for 5.2% of all cancers worldwide and 7.7% of all cancers in developing countries [1, 2]
We previously demonstrated that the zinc tetra-ascorbo-camphorate molecule, a monoterpenoid synthetic derivative, has a potent anti-HIV-1 in vitro activity [17]
The zinc tetra-ascorbo-camphorate molecule belongs to the heterogenous family of terpenoids, which is abundant, diverse in nature, extracted from various plants or obtained by chemical synthesis, and which comprises several characterized therapeutic agents having a large array of pharmacological properties such as anticancer, analgesic, antiinflammatory, immunomodulatory, and antiviral activities [11, 15, 16]

Summary

Introduction

Human papillomavirus (HPV) infection is the most common viral sexually transmitted infection worldwide and high risk-HPV (HR-HPV) genotypes, HPV-16 and HPV-18, are responsible for 5.2% of all cancers worldwide and 7.7% of all cancers in developing countries [1, 2]. The prophylactic vaccination with Gardasil-9® vaccine (Merck & Co. Inc., Kenilworth, NJ, USA) containing virus-like particles from HPV-6 and HPV-11, as well as two α7 (HPV-18 and HPV-45) and five α9 (HPV-16, -31, -33, -52 and -58) high-risk HPV, constitutes one of the main strategies against cervical cancer [5, 6], and is subsidized in underserved and poor countries by Global Alliance for Vaccines and Immunization [7]. It is increasingly recognized that the best strategy to prevent HPV infections should combine prophylactic vaccination in addition to topical antiviral chemoprophylaxis [9, 10]. Molecules used as topical broad-spectrum microbicides targeting HPVs could be useful in preventing HPV sexual transmission, in addition to the prophylactic vaccination [9]

Methods

Results

Discussion

Conclusion