Tucaresol: An Oral Candidate Drug With Two Distinct Antiviral Mechanisms.

Abstract

Abstract: Approximately 39 million people worldwide are living with Human Immunodeficiency Virus, HIV. However, the number of HIV infections is unevenly distributed with two thirds of global infections confined to Sub-Saharan Africa. Due to viral drug resistance, the most effective treatment requires a triple drug combination thereby adding to the complexity and cost of therapy. As such, many people living with HIV or at risk of infection do not have access to prevention or treatment of this potentially fatal disease. There is no cure for HIV [1]. Tucaresol is an orally active clinical stage drug which functions as a host targeted antiviral agent by controlled stimulation of CD4+ T helper immune cells. We report herein that Tucaresol also displays in-vitro activity against HIV. Although this antiviral activity is not potent, the excellent safety profile and bioavailability of Tucaresol, along with its low Molecular Weight, support attainment of relevant drug concentrations in man to achieve significant in-vivo activity. This is demonstrated by previously reported stabilization of viremia in a prior proof of concept phase 1b/2a HIV clinical trial [2]. It is possible that the significant in-vivo activity of Tucaresol arises from synergy between co-stimulation of CD4+ T helper cells and the direct activity against virally infected cells. A pan in-vitro viral screen of Tucaresol further revealed a weak, direct antiviral activity against human herpes virus 6B, human papillomavirus 11, measles virus and hepatitis B virus.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

This study did not receive any funding

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Human subjects were not recruited for any part of this study. Human PBMCs were isolated from whole blood buffy coats purchased from BioIVT.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

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I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

Data Availability

All data produced in the present study are available upon reasonable request to the authors

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