In silico Drug Repurposing of Anticancer Drug 5-FU and Analogues Against SARS-CoV-2 Main Protease: Molecular Docking, Molecular Dynamics Simulation, Pharmacokinetics and Chemical Reactivity Studies.

Background: Since the last COVID-19 outbreak, several approaches have been given a try to quickly tackle this global calamity. One of the well-established strategies is the drug repurposing, which consists in finding new therapeutic uses for approved drugs. Following the same paradigm, we report in the present study, an investigation of the potential inhibitory activity of 5-FU and nineteen of its analogues against the SARS-CoV-2 main protease (3CLpro).

Identification of potential inhibitors of SARS-CoV-2 main protease from compounds: A molecular docking study.

SARS-CoV-2 is the pathogen agent of the new corona virus disease that appeared at the end of 2019 in China. There is, currently, no effective treatment against COVID-19. We report in this study a molecular docking study of ten molecules with the main protease (3CLpro) responsible for the replication of coronaviruses.

α-methylation and α-fluorination electronic effects on the regioselectivity of carbonyl groups of uracil by H and triel bonds in the interaction of U, T and 5FU with HCl and TrH (Tr = B, Al).

Quantum chemical calculations at the ωB97XD/6-311++G(d,p) level of theory have been executed to investigate the effect of substituents via hydrogen-bonded and triel-bonded complexes between uracil (U), thymine (T) and 5-fluorouracil (5FU) with HCl for the former complexes, and with BH and AlH for the latter complexes. These calculations are supported by single-point energy calculations at MP2/6-311++G(d,p) and CCSD/6-31 + G(d,p) levels of theory, Natural Bond Orbital (NBO) and Molecular Electrostatic Potentials (MEPs) analyses, and global/local reactivity descriptors. The results reveal that triel-bonded complexes are strongly bounded than hydrogen-bonded ones, and Al-containing dimers stronger than B-containing ones.