Interactions Between Remdesivir, Ribavirin, Favipiravir, Galidesivir, Hydroxychloroquine and Chloroquine with Fragment Molecular of the COVID-19 Main Protease with Inhibitor N3 Complex (PDB ID:6LU7) Using Molecular Docking

Abstract

We started a study on the molecular docking of six potential pharmacologically active inhibitors compounds that can be used clinically against the COVID-19 virus, in this case, remdesivir, ribavirin, favipiravir, galidesivir, hydroxychloroquine and chloroquine interacting with the main COVID-19 protease in complex with a COVID-19 N3 protease inhibitor. The highest values of affinity energy found in order from highest to lowest were chloroquine (CHL), hydroxychloroquine (HYC), favipiravir (FAV), galidesivir (GAL), remdesivir (REM) and ribavirin (RIB). The possible formation of hydrogen bonds, associations through London forces and permanent electric dipole were analyzed. The values of affinity energy obtained for the hydroxychloroquine ligands was −9.9 kcal/mol and for the chloroquine of −10.8 kcal/mol which indicate that the coupling contributes to an effective improvement of the affinity energies with the protease. Indicating that, the position chosen to make the substitutions may be a pharmacophoric group, and cause changes in the protease.

3CLpro and PLpro affinity, a docking study to fight COVID19 based on 900 compounds from PubChem and literature. Are there new drugs to be found?

“…As previously mentioned, acquired docking results were compared to several published papers [ 11 , [13] , [14] , [15] , [16] , [17] , [18] , [19] , [20] , [21] , [22] ] in order to better ascertain the compound inhibitory potential against both SARS-Cov-2 proteases. Compounds that were found in these works as well as within the already downloaded set of compounds from the PubChem database include among others well-known antivirals such as Ribavirin, Oseltamivir, Darunavir, Remdesivir or the antimalarial drug Chloroquine etc., see Table 2 .…”

“… a) Docking scores from Fischer et al [13] b) Docking scores from Wu et al [11] c) Docking scores from Hosseini et al [16] d) Docking scores from Hall et al [15] e) Docking scores from Owis et al [19] f) Docking scores from Narkhede et al [18] g) Docking scores from Silva Arouche et al [20] h) Docking scores from Adem et al [17] i) Docking scores from Shah et al [21] , expressed as an average of up to five docking scores against 3CL pro structures (5R7Y, 5R7Z, 5R80, 5R81, 5R82) …”

“…Relatively high affinity towards both protein targets was also observed for Vazegepant/zavegepant, indicating that these compounds could be used as potential multi-targeting drugs. It is worth noting that many drugs that were discussed as possible SARS-CoV-2 M pro inhibitors, such as Remdesivir, chloroquine and hydroxy-chloroquine have not achieved outstanding docking scores [ 11 , 15 , 16 , [18] , [19] , [20] ].…”

“…Docking protocols were followed by molecular dynamics simulations of most promising compound-protein complexes to ascertain their conformational stability, and by the evaluation of free energy of binding. Several in silico research papers have been published over the previous year focusing either on docking studies [ 11 , [13] , [14] , [15] , [16] , [17] , [18] , [19] , [20] , [21] , [22] ] of selected compounds or screening a large number of compounds from external databases utilizing machine learning approaches [23] or virtual screening [24] . Our obtained results were compared with previously published papers [ 11 , [13] , [14] , [15] , [16] , [17] , [18] , [19] , [20] , [21] , [22] ] and redocking of several compounds with high affinity towards SARS-Cov-2 proteases from these works was performed to allow for a direct comparison to the presented results.…”

Inhibitory Potential Of Black Seed (Nigella Sativa L.) Bioactive Compounds Towards Main Protease Of SARS-CoV-2 : In Silico Study

“…One patient in the United States was given remdesivir on the 11th day since onset and gave a gradually improving response to clinical symptoms (Cao et al, 2020). However, the antiviral activity of these four compounds has not been reported to be specifically related to Mpro of SARS-CoV-2, but several in silico studies have also been conducted on these compounds to target Mpro (da Silva Arouche et al, 2020;Narkhede et al, 2020).…”