Randomized double-blind clinical study in patients with COVID-19 to evaluate the safety and efficacy of a phytomedicine (P2Et)

Abstract

BackgroundIt has been proposed that polyphenols can be used in the development of new therapies against COVID-19, given their ability to interfere with the adsorption and entrance processes of the virus, thus disrupting viral replication. Seeds from Caesalpinia spinosa, have been traditionally used for the treatment of inflammatory pathologies and respiratory diseases. Our team has obtained an extract called P2Et, rich in polyphenols derived from gallic acid with significant antioxidant activity, and the ability to induce complete autophagy in tumor cells and reduce the systemic inflammatory response in animal models.MethodsIn this work, a phase II multicenter randomized double-blind clinical trial on COVID-19 patients was designed to evaluate the impact of the P2Et treatment on the clinical outcome and the immunological parameters related to the evolution of the disease. The Trial was registered with the number No. NCT04410510*. A complementary study in an animal model of lung fibrosis was carried out to evaluate in situ lung changes after P2Et in vivo administration. The ability of P2Et to inhibit the viral load of murine and human coronaviruses in cellular models was also evaluated.ResultsPatients treated with P2Et were discharged on average after 7.4 days of admission vs. 9.6 days in the placebo group. Although a decrease in proinflammatory cytokines such as G-CSF, IL-15, IL-12, IL-6, IP10, MCP-1, MCP-2 and IL-18 was observed in both groups, P2Et decreased to a greater extent G-CSF, IL-6 and IL-18 among others, which are related to lower recovery of patients in the long term. The frequency of T lymphocytes (LT) CD3+, LT double negative (CD3+CD4-CD8-), NK cells increased in the P2Et group where the population of eosinophils was also significantly reduced. In the murine bleomycin model, P2Et also reduced lung inflammation and fibrosis. P2Et was able to reduce the viral replication of murine and human coronaviruses in vitro, showing its dual antiviral and anti-inflammatory role, key in disease control.ConclusionsTaken together these results suggest that P2Et could be consider as a good co-adjuvant in the treatment of COVID-19.Clinical trail registrationhttps://clinicaltrials.gov/ct2/show/NCT04410510, identifier: NCT04410510.

Plant extracts modulate cellular stress to inhibit replication of mouse Coronavirus MHV-A59

“…In a study mirroring observations in the MHV-A59 mouse model, both P2Et extract and Anamu SC were found to inhibit COVID-19 viral replication in Vero E6 cells from patient isolates. A Phase II clinical trial in COVID-19 patients treated with P2Et demonstrated a 2.7 day earlier hospital discharge compared to the placebo group, accompanied by a significant reduction in pro-inflammatory cytokines [ 20 ]. These findings suggest that these natural extracts, particularly P2Et, can effectively treat human coronavirus infections.…”

“…In vitro experiments using Vero E6 cells revealed a significant inhibition of viral replication by both extracts. Subsequently, a phase II multicentric randomized, double-blind clinical trial was conducted to assess the impact of P2Et treatment on clinical outcomes and immunological response in COVID-19 patients [ 20 ].…”

Effectiveness of Drug Repurposing and Natural Products Against SARS-CoV-2: A Comprehensive Review

“…In mice injected with bleomycin, P2Et also decreased lung inflammation, fibrosis, and replication of human coronaviruses in vitro, showing its antiviral activity and anti-inflammatory capacity, two essential mechanisms to control the disease. 184 …”

Plant-derived extracts and metabolic modulation in leukemia: a promising approach to overcome treatment resistance

“…The central research area of our group is the study and development of phytomedicines from Colombian plants, among them Petiveria alliacea (P. alliacea), Caesalpinia spinosa (C. spinosa), Tillandsia usneoides (T. usneoides), and Piper nigrum (P. nigrum) (Lasso et al, 2018;Urueña et al, 2020;Lasso et al, 2022;Urueña et al, 2022). Each one of the extracts of these plants has been characterized from a chemical point of view, and the main compounds have been isolated and studied.…”

“…The extracts are standardized to be developed as botanical drugs due to their interesting antitumor and immunomodulatory activity in animal models (Lasso et al, 2018;Urueña et al, 2020). C. spinosa has also been studied in normal individuals to assess its safety and in coronavirus disease 2019 (COVID-19) patients, where significant biological activity has been demonstrated (Duran et al, 2022;Urueña et al, 2022).…”