<p></p><p>Despite strict measures taken by
many countries, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
continues to be an issue of global concern. Currently, there are no clinically
proven pharmacotherapies for coronavirus disease 2019, despite promising
initial results obtained from drugs such as azithromycin and hydroxyquinoline.
Therefore, the repurposing of clinically approved drugs for use against
SARS-CoV-2 has become a viable strategy. Here, we searched for drugs that
target SARS-CoV-2 3C-like protease (3CL<sup>pro</sup>) and viral RNA-dependent
RNA polymerase (RdRp) by in silico
screening of the U.S. Food and Drug Administration approved drug library.
Well-tolerated and widely used drugs were selected for molecular dynamics (MD)
simulations to evaluate drug-protein interactions and their persistence under
physiological conditions. Tetracycline, dihydroergotamine, ergotamine,
dutasteride, nelfinavir, and paliperidone formed stable interactions with 3CL<sup>pro</sup>
based on MD simulation results. Similar analysis with RdRp showed that
eltrombopag, tipranavir, ergotamine, and conivaptan bound to the enzyme with
high binding free energies. Docking results suggest that ergotamine,
dihydroergotamine, bromocriptine, dutasteride, conivaptan, paliperidone, and
tipranavir can bind to both enzymes with high affinity. As these drugs are well
tolerated, cost-effective, and widely used, our study suggests that they could
potentially to be used in clinical trials for the treatment of
SARS-CoV-2-infected patients.</p><br><p></p>