Preprint Review Version 3 Preserved in Portico This version is not peer-reviewed

Tucaresol: A Unique Oral Candidate Drug Ideally Accessible for Treatment of COVID-19 Disease

Version 1 : Received: 9 November 2022 / Approved: 11 November 2022 / Online: 11 November 2022 (07:52:38 CET)
Version 2 : Received: 28 November 2022 / Approved: 28 November 2022 / Online: 28 November 2022 (07:29:24 CET)
Version 3 : Received: 11 March 2023 / Approved: 14 March 2023 / Online: 14 March 2023 (08:51:05 CET)

A peer-reviewed article of this Preprint also exists.

Penney, C. L., Zacharie, B., Duceppe, J. S. (2023). Tucaresol: A Unique Oral Candidate Drug Ideally Accessible for Treatment of COVID-19 Disease. Journal of Clinical Review & Case Reports, 8(4), 74-83. Penney, C. L., Zacharie, B., Duceppe, J. S. (2023). Tucaresol: A Unique Oral Candidate Drug Ideally Accessible for Treatment of COVID-19 Disease. Journal of Clinical Review & Case Reports, 8(4), 74-83.


Abstract: The SARS-CoV-2 pandemic has significantly impacted world health and economic status. In response, much work has been undertaken to provide effective, safe vaccines, antibodies and antiviral drugs with which to address this pandemic. Treatment of a pandemic population presents multiple challenges in addition to the primary issue of drug efficacy and safety, such as large scale drug manufacture and distribution, drug stability, oral dosing and pharmacoeconomic considerations. Ideally, these factors must be addressed if new candidate drugs are to be advanced for treatment of large (pandemic) populations. Subsequently, new antivirals have reached the market but choices are few. According to the NIH Covid Treatment Guidelines, only three small molecule antiviral drugs are available to treat COVID-19 disease. As such, a significant part of the research towards discovery of new antiviral drugs has focused on screening and evaluation of ‘repurposed drugs’ or previously approved or clinical stage drugs. Yet, in spite of this increased research activity, one promising clinical stage candidate drug has received little attention regarding its potential as a monotherapy or component of combination therapy for treatment of COVID-19 disease. Tucaresol, with documented human safety and pharmacokinetic data, is an orally active, stable, small molecule amenable to large scale manufacture by a proprietary two-step synthesis developed by us. Tucaresol functions as a host-targeted antiviral by selective protection/reconstitution of CD4+ T helper cells as demonstrated in HIV patients and SIV macaques. In view of similarities between HIV and SARS-CoV-2, especially with respect to host CD4+ T helper cells, and the suitability of Tucaresol for facile treatment of pandemic populations, Tucaresol is presented herein for treatment of mild-to-moderate COVID-19 patients but may also be useful for treatment of advanced disease accompanied by lymphopenia.


Tucaresol; COVID-19; SARS-CoV-2; HIV; T helper cell; CD4 receptor


Medicine and Pharmacology, Pharmacology and Toxicology

Comments (1)

Comment 1
Received: 14 March 2023
Commenter: Jean-Simon Duceppe
Commenter's Conflict of Interests: Author
Comment: Comment: With over 400 views of our preprint to-date, we gratefully acknowledge the attention regarding the candidate drug Tucaresol as a potential treatment for covid-19 disease. The purpose of this article is to convince the reader that amongst the many approved and clinical stage drugs that have been studied for treatment of covid-19 disease and briefly reviewed in this article, Tucaresol, initially targeted for treatment of HIV, accumulated enough clinical, preclinical and research data to warrant examination as a treatment for covid-19 disease. Furthermore, the case is made that Tucaresol is likely best suited for combination therapy with another antiviral agent with a mechanism that is distinct from Tucaresol. Currently there are still few choices. Apparently Pfizer is not pursuing combination therapy with Paxlovid and Tucaresol or an alternative drug but instead is pursuing a new viral protease inhibitor. Further clinical trials with Lagevrio (Merck, not reported in version 3) have not provided significantly improved antiviral data and the ongoing clinical trial of the potent antiviral candidate drug EDP-235 (Enanta) has required 2 phase 1 drug-drug interaction clinical trials with results apparently not yet published. The Shionogi antiviral protease inhibitor, Ensitrelvir, recently approved in Japan will not be available in North America in the near future. Nonetheless, new information is presented regarding omicron virus variants and their ability to evade humoral (antibody binding) immunity along with other aspects of increased virus infectivity, as exemplified by increased pathogenicity upon repeated covid-19 disease along with the recent observation of increased norovirus, RSV and influenza virus infections this winter.Christopher Penney, Ph.D.
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