Ensaios clínicos de fármacos no tratamento de Covid-19 e prediçãode um epítopo racionalmente selecionado da proteína do envelope viral

Abstract

According to the World Health Organization (WHO), in the first month of 2022 there were about 300 million confirmed cases of COVID-19, a respiratory disease caused by the SARS-CoV-2 virus that has caused more than 5,900,000 deaths worldwide. . A pandemic was declared by the WHO in March 2020, when the new coronavirus spread around the world and new variants are making it difficult to control infections. The short time between the first cases in Wuhan and the declaration of a pandemic started the search for ways to stop the spread of SARS-CoV-2 or to try to cure the disease COVID- 19. More than ever, research groups are developing vaccines, drugs and immunobiological compounds, they are also trying to reposition existing drugs in an increasing number of clinical trials. There are great expectations regarding prophylaxis through vaccines around the world that have already proven to be effective for the prevention of COVID-19. However, producing sufficient doses of vaccines, equitable availability for the entire world population, and the emergence of new variants of SARS- CoV-2 are increasingly observed challenges. Despite this, efforts have been made to create different vaccines with different approaches so that they can be used by the entire population. In this work, we summarize about 3,743 clinical trials in different phases, showing a greater number of clinical trials based on drug development or repositioning studies in Europe and the USA and fewer clinical trials in low-income countries. Promising results on the repositioning and development of new drugs, monoclonal antibodies, convalescent plasma and mesenchymal stem cells to control viral infection/replication or the hyperinflammatory response of the host to the new coronavirus, bringing hope for the treatment of the disease. In this context, the structural proteins of the new coronavirus, such as the viral envelope protein (E), are promising as specific molecular targets in the search for drugs or even in the identification of immunostimulants. Thus, in this work we also aimed to identify immunostimulatory epitopes in the SARS-CoV-2 envelope protein. Using the NCBI SARS-CoV-2 Resources database, 53,838 deposited genomes of the new coronavirus were used to identify the gene encoding the E protein, followed by in silico translation and overlapping sequences of the 75 amino acids of this protein to identify a consensus E protein world. This sequence was used for the identification by molecular modeling of the three-dimensional structure and for in silico analysis of potential immunostimulatory epitopes capable of being presented via MHC-I or MHC-II or recognized by BCRs, and of the physicochemical and molecular docking with MHC molecules, a promising linear epitope of the E protein was identified: LVKPSFYVYSRVKNLNS. In vitro and in vivo assays must be performed to confirm the results obtained in silico so that this peptide can potentially be used as a vaccine component or even as a molecular target for diagnosing the presence of infection caused by SARS-CoV-2.