This research will computationally study the influence of pH on the SARS-CoV-2 and SARS-CoV virus receptors. the objective will be to find out which pH is the most suitable for each complex, and which will allow greater spontaneity in the interaction between the drug and the receptors involved in viral replication.
According to the World Health Organisation, on April 19, 2020, the number of confirmed cases of COVID-19 had already surpassed the mark of 2 240 000, with about 152 000 confirmed deaths worldwide. In Brazil, these numbers translated into 36 929 in patients affected by the virus and 2 372 deaths, with community transmission of COVID-19 throughout the national territory. The new beta-Coronavirus has been causing immense losses worldwide, in different aspects. Researches have indicated a correlation between the potential for inhibition of the SARS-CoV virus and the physiological pH of the cellular microenvironment. This research will computationally study the influence of pH on the SARS-CoV-2 and SARS-CoV virus receptors. Among the drugs researched for the remission of symptoms, Chloroquine and its derivatives, have stood out as potential for treatment. However, many doubts and contradictions still remain. In this research, we will seek to understand how the physiological pH of the different subcellular compartments can affect the protonation state of the receptor-ligand complex, and consequently the free energy value of interaction. Thus, the objective will be to find out which pH is the most suitable for each complex, and which will allow greater spontaneity in the interaction between the drug and the receptors involved in viral replication. The protonation and addition of partial charges will be calculated varying pH conditions in range 4.0-9.0. The structures will be optimized with mechanical-quantum calculations. Molecular docking simulations will be performed to understand the correlation dependence between the pH value and free energy. Classical molecular dynamics simulations will also be employed to better understand the conformational changes in the complex. ADMET studies will be conducted to understand which Chloroquine derivatives are safer and more effective in treatment.