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

Seref Gul, Onur Ozcan, Sinan Asar, Alper Okyar, Ibrahim Barıs, Ibrahim Halil Kavakli

10.1080/07391102.2020.1802346

Research curated

Abstract

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.

Source: PubMed

Related molecules

Name	Synonyms	Genes
Paliperidone
Conivaptan
RNA dependent RNA polymerase	RDR, viral RNA polymerase, RdRp, nsp12	rep, ORF1a-1b, RdRp
Tipranavir
Ergotamine
Nelfinavir
Dihydroergotamine
3C-like protease	3CLpro, Mpro, SARS coronavirus main peptidase, 3CLpro-SARS-CoV-2	rep, ORF1a-1b
Eltrombopag
Dutasteride

Related interactions

Target	Drug	Type	Result
3C-like protease	Dutasteride	Computational	positive
3C-like protease	Paliperidone	Computational	positive
RNA dependent RNA polymerase	Tipranavir	Computational	positive
RNA dependent RNA polymerase	Nelfinavir	Computational	positive
RNA dependent RNA polymerase	Dihydroergotamine	Computational	positive
RNA dependent RNA polymerase	Conivaptan	Computational	positive
RNA dependent RNA polymerase	Dutasteride	Computational	positive
RNA dependent RNA polymerase	Eltrombopag	Computational	positive
3C-like protease	Conivaptan	Computational	positive
3C-like protease	Ergotamine	Computational	positive
3C-like protease	Nelfinavir	Computational	positive
3C-like protease	Dihydroergotamine	Computational	positive