According to the World Health Organisation, until 16 June, 2020, the number of confirmed and notified cases of COVID-19 has already exceeded 7.9 million with approximately 434 thousand deaths worldwide. This research aimed to find repurposing antagonists, that may inhibit the activity of the main protease (Mpro) of the SARS-CoV-2 virus, as well as partially modulate the ACE2 receptors largely found in lung cells, and reduce viral replication by inhibiting Nsp12 RNA polymerase. Docking molecular simulations were performed among a total of 60 structures, most of all, published in the literature against the novel coronavirus. The theoretical results indicated that, in comparative terms, paritaprevir, ivermectin, ledipasvir, and simeprevir, are among the most theoretical promising drugs in remission of symptoms from the disease. Furthermore, also corroborate indinavir to the high modulation in viral receptors. The second group of promising drugs includes remdesivir and azithromycin. The repurposing drugs HCQ and chloroquine were not effective in comparative terms to other drugs, as monotherapies, against SARS-CoV-2 infection.

The novel β-coronavirus has caused sad losses worldwide and the emergence of new variants has been causing great concern. Thus throughout this research, the lineage B.1.1.28 of clade P.2 (K417N, N501Y, E484K) that emerged in Brazil was studied but also in a less depth the P.1 lineage, where through simulations of molecular dynamics in the NAMD 3 algorithm in the 8 ns interval it was possible to understand the thermodynamic impacts in the interaction of the ACE2-RBD complex and the neutralizing antibody RBD-IgG. From the molecular dynamics, we noticed that the RMSF averages in the P.2 strain were more expressive in comparison to the ACE2-RBD wild-type and consequently some regions have undergone more expressive conformational changes although, in general, a greater stabilization of the complex was perceived. In addition, was an increase in the average number of Hydrogen bonds generating a lower RMSD and greater system compaction measured by Radius of Gyration (Rg). The change in native contacts was also important where the decrease from 0.99(2) to 0.98(8) reflects structural changes, which could reflect in greater transmissibility and difficulty in recognizing neutralizing antibodies. Through the MM-PBSA decomposition, we found that Van der Waals interactions predominated and were more favorable when the structure has mutations of the P.2 lineage. Therefore we believe that the greater stabilization of the ACE2-RBD complex may be a plausible explanation of why some mutations are converging in different lineages such as E484K and N501Y.