Abstract
At the end of 2019, the world was struck by the COVID-19 pandemic, which resulted in dire repercussions of unimaginable proportions. From the beginning, the international scientific community employed several strategies to tackle the spread of this disease. Most notably, these consisted of the development of a COVID-19 vaccine and the discovery of antiviral agents through the repositioning of already known drugs with methods such as de novo design. Previously, methylthiomorphic compounds, designed by our group as antihypertensive agents, have been shown to display an affinity with the ACE2 (angiotensin converting enzyme) receptor, a key mechanism required for SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) entry into target cells. Therefore, the objective of this work consists of evaluating, in silico, the inhibitory activity of these compounds between the ACE2 receptor and the S1 subunit of the SARS-CoV-2 spike protein. Supported by the advances of different research groups on the structure of the coronavirus spike and the interaction of the latter with its receptor, ACE2, we carried out a computational study that examined the effect of in-house designed compounds on the inhibition of said interaction. Our results indicate that the polyphenol LQM322 is one of the candidates that should be considered as a possible anti-COVID-19 agent.
Highlights
In December 2019, a new type of disease has been reported in the city of Wuhan (Hubei Province, China), where many cases of atypical pneumonia were diagnosed [1]
Its genome is about 30 kilobases in length and contains a 5 untranslated region (UTR) and a 3 poly(A)-tail at the 3 UTR, allowing it to have a similar structure to the host cell mRNAs [5,6,7]
Processes that refer to ACE2–In complexes, the RMSD, RMSF, and the total hydrogen bonds of the protein were all analyzed during simulation, as well as the hydrogen bonds formed between the ligand and the protein, and the free energy of binding
Summary
In December 2019, a new type of disease has been reported in the city of Wuhan (Hubei Province, China), where many cases of atypical pneumonia were diagnosed [1]. The emergence and expansion of SARS-CoV-2 has caused immeasurable damage to the global health and economy sectors, which is why it is of great importance for all countries to collaborate to fight against this deadly disease. Its genome is about 30 kilobases (kb) in length and contains a 5 untranslated region (UTR) and a 3 poly(A)-tail at the 3 UTR, allowing it to have a similar structure to the host cell mRNAs [5,6,7] Besides both 5 and 3 UTRs, its genome contains the overlapping ORF1a and 1b genes that encode 15–16 non-structural proteins (nsps), many of which assemble into a replication/transcription complex (RTC) [8]. Viral structural proteins, including the spike (S), envelope (E), membrane (M), and nucleocapsid (N), as well as other accessory proteins, are encoded in the genes downstream of ORF1a/ORF1b [9]
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