In Silico Identification of Widely Used and Well Tolerated Drugs That May Inhibit SARSCov- 2 3C-like Protease and Viral RNA-Dependent RNA Polymerase Activities, and May Have Potential to Be Directly Used in Clinical Trials

We performed repurposing of FDA approved drugs against SARS-CoV-2 3 chymotrypsin like protease and RNA-dependent RNA polymerase. During the screening, 3948 drugs approved by the U.S. Food and Drug Administration (FDA) to target the active site of 3CLpro and nsp8 binding sites of RdRp and, in turn, disturb SARS-CoV-2 life cycle in host cell. As a result of molecular docking and molecular

dynamics simulations, several drugs with high binding affinity to both SARS-Cov-2 3CLpro and RdRp targets were identified. While drugs such as tetracycline and its derivatives, dihydroergotamine, ergotamine, dutasteride, nelfinavir, paliperidone, and conivaptan were identified to bind SARS-Cov-2 3CLpro; tipranavir, nelfinavir, dihydroergotamine, conivaptan, dutasterid and eltrombopag were found to bind nsp8 binding site of RdRp. Notably, further analysis of the results showed that ergotamine,

dihydroergotamine, conivaptan, paliperidone, and tipranavir can bind to both enzymes with high affinity. Since these drugs are well tolerated, cost-effective and widely used, our study suggested that tetracycline and its derivatives, dutasteride, ergotamine, bromocriptine, tipranavir, conivaptan, paliperidone, eltrombopag drugs have the potential to be used alone or in combination as adjuvant for

the treatment of SARS-CoV-2 infected patients.