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. 2021 Jun 6;7(6):e07232.
doi: 10.1016/j.heliyon.2021.e07232. eCollection 2021 Jun.

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

Ralph Sydney Mboumba Bouassa  1   2   3 , Bernard Gombert  4 , Gabin Mwande-Maguene  5 , Aurèle Mannarini  4 , Laurent Bélec  2   3
Affiliations

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

Ralph Sydney Mboumba Bouassa et al. Heliyon. .

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.

Keywords: Camphor derivates; HPV; HPV-16; Inhibition assay; L-ascorbic acid conjugate; Pseudovirus; Terpenoid; Zn metal.

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Conflict of interest statement

The authors declare the following conflict of interests: Ralph Sydney Mboumba Bouassa, Gabin Mwande-Maguene and Laurent Bélec report no conflicts of interest. Bernard Gombert, the chief executive officer of MGB Pharma, Nîmes, France, gave the C14 molecule for the study. Aurèle Mannarini is chemist adviser for MGB Pharma, and discussed the interpretation of the results. Bernard Gombert and Aurèle Mannarini did not play a role in the study design, data collection and analysis, as well as decision to publish.

Figures

Figure 1
Figure 1
Cram's structure of the neutral (A) and ionic (B) forms of zinc tetra-ascorbo-camphorate 4(C6H6O6)Zn(C10H14O4). The C14 structure comprises a pentacyclic ring including a comphorate terpene [generic formula: (C5H8)n] and 4 L-ascorbic acids stably associated with an unique Zn metal. The box depicts a condensed form of the chemical structure of the C14 molecule solubilized in aqueous or physiologic environments providing aqueous complex negatively charged.
Figure 2
Figure 2
Evaluation of C14 toxicity on COS-7 cells. COS-7 cells were cultured with increased concentrations of C14 for 24 h. After washing, culture viability was determined by using the MTT-cytotoxicity assay according to the manufacturer's instructions. The values given are the mean viability ±1 standard deviation of COS-7 cells, expressed in percentage. Means ± SD are representative of 3 independent experiments.
Figure 3
Figure 3
Evaluation of C14 inhibitory activity on HPV-16-PsVs adsorption on COS-7: (A) HPV-16-PsVs was added in culture medium after 3 h preincubation with serial C14 dilutions; (B) HPV-16-PsVs and C14 dilutions were added simultaneously. Pooled sera from individuals having received three doses of Gardasil-9® vaccine (Merck & Co. Inc.) used as positive control showed luminescence signal inhibition above 80% (not shown). The anti-HPV-16-PsVs IC50 values (shown as a vertical dotted line) were estimated using the luciferase inhibitory assay in COS-7 cells by the GraphPad Prism v5.04 software (GraphPad Software). Means ± SD are representative of 3 independent experiments. Therapeutic indexes (TI = CC50/IC50) were between >410 to >3,330.
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