Knowledge and chemical valuation of the Caribbean Pharmacopoeia against COVID-19

Project display Our particular approach to the Coronavirus (COVID-19) crisis is to study the Caribbean Pharmacopoeia, in order to select a list of plants that can be tested against COVID. Once selected, the plants will undergo a chemical extraction procedure and in silico screening to finish with an in vitro study of its activity against COVID-19. The molecules showing activity against the virus will be tested for the treatment of cellulosic supports (masks). At the same time, we will try to develop a COVID-19 screening method. Goals The main objectives of the project are organized into three axes: Axis 1 "Ethnopharmacology" This axis consists in the study of the Caribbean Pharmacopoeia as a source of new compounds against COVID-19 (SARS-CoV-2). In collaboration with the Autonomous University of Barcelona, ​​and the 100% ZEB and APLAMEDAROM associations. The objectives in this axis are: Make a selection of potentially interesting medicinal plants as anti-COVID agents. This selection will be made according to three criteria: Pharmacological activity postponed in the face of respiratory diseases (influenza, colds, pneumonia, bronchitis, asthma or bacteria) described in the Caribbean Pharmacopoeia. Anti-malaria pharmacological activity. The infectious disease specialist Didier Raoult, from the Institut Hospitalo-Universitaire de Marseille, recently presented the results of a first clinical trial on the treatment of the coronavirus with two molecules: chloroquine (Nivaquine®) and its derivative, hydroxy chloroquine (Plaquenil®). Finally, we will look in the Caribbean Pharmacopoeia for plants having the same properties as chloroquine ("plants-chloroquine-like"). Antiviral and immunostimulant activity described in the bibliography. This selection would be made in collaboration between the COVACHIM-M2E laboratory, and the APLAMEDAROM and 100% ZEB associations. Eco-production of extracts. The plants of the Caribbean plant pharmacopoeia will be screened according to these 3 criteria and the selected plants will be worked for the production of "green" extracts: ethanolic (EtOH), aqueous (H2O), hydroalcoholic (H2O / EtOH) and essential oils (when is possible). Screening in silico. The list of compounds likely to appear in previous research will be large. For the continuation of the project, it is important to be able to reduce its size, in particular by determining the elements of greatest potential affinity to the therapeutic objectives of COVID-19. A first step will consist of in silico studies for the prediction of the best candidate molecules to interact with biological macromolecules. These calculations will be performed instead by Protein-Ligand Docking methods, a family of fundamental methods in medicinal chemistry and drug development on the main protease of COVID-19 (Mpro) 2 Axis 2 "electrochemical screening", enzyme which allows the virus to replicate indefinitely. Compounds with the best theoretical profile will be subjected to molecular dynamics simulations and binding free energy calculations. It is important to mention that the INSILICHEM laboratory recently worked intensively on the same protease with compounds from South American medicinal plants (manuscript in revision). Axis 3 "Treatment of cellulosic surfaces" will be used to carry out a first study of bioactivity and to select the potentially active extracts / molecules. For this, positive samples from patients will be pooled to obtain 5 ml of positive samples and 5 ml of negative samples. All these samples are diluted in physiological serum. The positive and negative 5 ml will be filtered through 0.48μ filters. PCR will be carried out on these filtrates to verify positivity and negativity. Obviously, these results will be supplemented by data from Axis 1. This axis consists of the treatment of cellulosic materials with extracts containing molecules of interest which will be modeled (chemo informatically) and tested on cellulosic supports. This axis will be developed by the COVACHIM-M2E laboratory and the chemo-informatics laboratory (Federal University of Paraíba). Based on the information gathered in axes 1 and 2, we will work on the development of a method for treating cellulosic materials.