The Colombian pill for Covid-19

Original Link https://www.javeriana.edu.co/pesquisa/colombiana-pildora-covid-19-pastilla/

Author: Paula Andrea Grisales 

The Colombian pill for covid-19 was achieved after more than 13 years of research. About 13 patents, a spin-off, and clinical studies result in a pill that reduces inflammation and increases the response in respiratory diseases such as COVID-19. This is the story of a phytomedicine with the signature of the Javeriana University.

This article, titled «The Colombian pill for Covid-19», was originally published under the title of «Encapsulated Scientific and Popular Knowledge», in the 59th edition of Pesquisa Javeriana.

Sometimes we dedicate enormous efforts to a purpose and then, due to the twists and turns that life takes, we obtain achievements in something else. Unexpected achievements that would not have been possible without the initial efforts, when the eventual outcome was unknown to us. It happens in life and it also happens in science. Some call it serendipity.

The treatment of breast cancer and leukemia from extracts of two plants used in traditional popular medicine has been the objective of the immunologist Susana Fiorentino Gómez. She has dedicated more than 13 years of work to this along with her Immunology and Cell Biology research group, from the Pontificia Universidad Javeriana, with whom she has obtained important achievements and recognitions. When they were about to start a clinical study to analyze how one of the extracts works combined with chemotherapy in breast cancer patients, the COVID-19 pandemic broke out, changing their plans. They decided to test the dividivi extract in patients with coronavirus, since the traditional use of this plant is precisely to treat respiratory conditions. The results were remarkable.

Thirteen compounds of the Colombian pill for covid-19

Five of the more than 13 years of work of the research group led by the immunologist Fiorentino have been focused on the study of the seeds of the dividivi tree (Caesalpinia spinosa), which grow mainly in Boyacá, in the upper Ricaurte region. Their interest began when Fiorentino discovered the anti-inflammatory power of the plant, since the farmers of Villa de Leyva (Boyacá) used it to treat sinusitis: “They make an infusion and smell it, the bad thing is that it damages their bones because it is very strong” . This led her to think that she could study it to treat cancer, due to its ability to modulate inflammation: «This biological effect is related to cancer control activity,» she explains.

During those years, she and her group acquired diverse knowledge about the development of a medicine from an extract of this plant, that is, a phytomedicine. They identified more than 13 molecules or compounds, which work together to achieve anti-inflammatory and anti-tumor effects. The dividivi extract was initially tested on tumor cells and showed that it can kill them; it was tested in 3D culture models in which it increased sensitivity to other chemotherapeutic agents; and decreased tumors in mice with breast cancer; it was then tested in healthy people through a phase 1 clinical study, where it was found to be safe.

When they were about to study this extract in combination with chemotherapy —thanks to funding from the Paces Program (Ecosistema Científico)—, the pandemic reoriented priorities: “We already knew how it acted on cells, on the immune system and how it regulated lung inflammation». That is where the phase 2 study was born to test the phytomedicine in patients with COVID-19, which was approved by the National Institute for Food and Drug Surveillance (Invima), and financed by the Mincienciatón call.

Extract versus placebo

After designing very rigorous research protocols, the experiment began. For 28 days each of the 91 people who agreed to be part of the clinical study was observed and evaluated in 150 parameters. Randomly, 44 patients received the phytomedicine for 14 days – one capsule every 12 hours -, while another 46 took a placebo. “It was a challenging process, because at the beginning of the pandemic many patients were wary due to misinformation,” explains Dr. María Margarita Manrique Andrade, director of the Research Office of the San Ignacio University Hospital, one of the centers where the study was carried out.

After resolving the difficulties in recruitment, the various analysis yielded surprising findings. The most notable indicated that those who took the capsule with dividivi extract had an average of 7,395 days of hospital stay, compared to 9,581 days for the placebo group, that is, 2,186 days less. This means that those who took the dividivi extract left the hospital two and a half days faster, that is, they recovered faster.

The researcher explains that this occurred, among other things, due to two key effects: the phytomedicine decreased viral replication because it increases intracellular cleaning, and it also decreased inflammation because it modulated the immune response that results in lung damage. But how does this happen?

The universe of cells

To understand viral replication, it is necessary to understand how cells normally act. They are like a small living being that breathes and does different activities. For example, they defend themselves when they detect that something foreign has entered inside them, in which case they trap it in a bag or vesicle and then expel it. But the virus prevents them from doing this cleaning process, called autophagy, so the virus manages to replicate until it breaks the cells and then goes out and infects others. What the extract did was increase cell autophagy and thus decrease viral replication.

On the other hand, inflammation is related to the messages that cells emit and receive. They communicate with signals and act. They have receptors on the cell membrane through which they receive signals, such as “I must change my route”, “I must divide”, “I must die”, etc. In this case, molecules called polyphenols, present in the phytomedicine, reach the cells in the lung and give them the message not to exaggerate the immune response, that is, not to produce proinflammatory cytokines; It is as if they were told: «Yes, we are in a battle with this virus, but let’s calm down, we don’t have to call in the whole army, it’s a trap.»

In an attack caused by the virus, the entire immune response arrives to heal the lung, but, since the virus is still present, the immune response does not heal, but instead increases lung damage. «The virus induces an exacerbated response, the immune system gets scared,» explains Dr. Fiorentino, adding: «The phytomedicine signals the cells of the immune response to tell them that this signaling pathway cannot be activated because otherwise the lung will be damaged; what is called the ‘translocation of the NF-kB factor’ is decreased, a protein that goes to the nucleus and gives the signal to produce pro-inflammatory cytokines. The phytomedicine decreases these signals”.

DreemBio, a benchmark for knowledge transfer

Although it is essential for the academy to synthesize research findings in scientific articles, books, or book chapters, there is an even greater challenge: ensuring that the knowledge effectively reaches society. The researcher Susana Fiorentino had been clear about this for years and, after exploring various paths, founded DreemBio, a technology-based company that bases its activity on the knowledge produced from the university, that is, a spin-off.

On this subject, Fiorentino recalls that it has not been an easy road, but after negotiations between Javeriana and DreemBio, the patents were finally transferred to the company in exchange for royalties and the possibility of joint work. «It has been a path that Dr. Susana has carved out, where other researchers see that good research can be done, protected through patents and transferred to create a company,» explains Mario Andrés Ortega Mendoza, an expert lawyer in intellectual property.

From various points of view, this case of basic research and knowledge transfer through a spin-off is a milestone for the country, and marks a path forward for Javeriana and other universities. It is a reference of the way in which, as a society, the step must be taken towards initiatives that manage to put knowledge outside the classrooms and laboratories to provide solutions and, as in the case of this dividivi extract capsule, save lives.

RESEARCH TITLE:

Efficacy and safety of P2Et extract in adjuvant treatment in patients with COVID-19

RESEARCHERS:  Susana Fiorentino, Ángel Alberto García, Alfonso Barreto, Claudia Urueña, Sandra Quijano, Alejandra Gómez Cadena, Ricardo Ballesteros et al. 

RESEARCH PERIOD: 2020-2021