Dataset Information

Virtual screening and repurposing of FDA approved drugs against COVID-19 main protease.

ABSTRACT:

Aims

In December 2019, the Coronavirus disease-2019 (COVID-19) virus has emerged in Wuhan, China. In this research, the first resolved COVID-19 crystal structure (main protease) was targeted in a virtual screening study by of FDA approved drugs dataset. In addition, a knowledge gap in relations of COVID-19 with the previously known fatal Coronaviruses (CoVs) epidemics, SARS and MERS CoVs, was covered by investigation of sequence statistics and phylogenetics.

Materials and methods

Molecular modeling, virtual screening, docking, sequence comparison statistics and phylogenetics of the COVID-19 main protease were investigated.

Key findings

COVID-19 Mpro formed a phylogenetic group with SARS CoV that was distant from MERS CoV. The identity% was 96.061 and 51.61 for COVID-19/SARS and COVID-19/MERS CoV sequence comparisons, respectively. The top 20 drugs in the virtual screening studies comprised a broad-spectrum antiviral (ribavirin), anti-hepatitis B virus (telbivudine), two vitamins (vitamin B12 and nicotinamide) and other miscellaneous systemically acting drugs. Of special interest, ribavirin had been used in treating cases of SARS CoV.

Significance

The present study provided a comprehensive targeting of the first resolved COVID+19 structure of Mpro and found a suitable save drugs for repurposing against the viral Mpro. Ribavirin, telbivudine, vitamin B12 and nicotinamide can be combined and used for COVID treatment. This initiative relocates already marketed and approved safe drugs for potential use in COVID-treatment.

SUBMITTER: Kandeel M

PROVIDER: S-EPMC7194560 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Publications

Virtual screening and repurposing of FDA approved drugs against COVID-19 main protease.

Kandeel Mahmoud M Al-Nazawi Mohammed M

Life sciences 20200403

<h4>Aims</h4>In December 2019, the Coronavirus disease-2019 (COVID-19) virus has emerged in Wuhan, China. In this research, the first resolved COVID-19 crystal structure (main protease) was targeted in a virtual screening study by of FDA approved drugs dataset. In addition, a knowledge gap in relations of COVID-19 with the previously known fatal Coronaviruses (CoVs) epidemics, SARS and MERS CoVs, was covered by investigation of sequence statistics and phylogenetics.<h4>Materials and methods</h4> ...[more]

PMID: 32251634

Similar Datasets

Project description:Coronaviruses are enveloped positive-strand RNA viruses belonging to family Coronaviridae and order Nidovirales which cause infections in birds and mammals. Among the human coronaviruses, highly pathogenic ones are Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) and the Middle East Respiratory Syndrome coronavirus (MERS-CoV) which have been implicated in severe respiratory syndrome in humans. There are no approved antiviral drugs or vaccines for the treatment of human CoV infection to date. The recent outbreak of new coronavirus pandemic, coronavirus disease 2019 (COVID-19) has caused a high mortality rate and infections around the world which necessitates the need for the discovery of novel anti-coronaviral drugs. Among the coronaviruses proteins, 3C-like protease (3CLpro) is an important drug target against coronaviral infection as the auto-cleavage process catalysed by the enzyme is crucial for viral maturation and replication. The present work is aimed at the identification of suitable lead molecules for the inhibition of 3CLpro enzyme via a computational screening of the Food and Drug Administration (FDA) approved antiviral drugs and phytochemicals. Based on binding energies and molecular interaction studies, we shortlisted five lead molecules (both FDA approved drugs and phytochemicals) for each enzyme targets (SARS-CoV-2 3CLpro, SARS-CoV 3CLpro and MERS-CoV 3CLpro). The lead molecules showed higher binding affinity compared to the standard inhibitors and exhibited favourable hydrophobic interactions and a good number of hydrogen bonds with their respective targets. A few promising leads with dual inhibition potential were identified among FDA approved antiviral drugs which include DB13879 (Glecaprevir), DB09102 (Daclatasvir), molecule DB09297 (Paritaprevir) and DB01072 (Atazanavir). Among the phytochemicals, 11,646,359 (Vincapusine), 120,716 (Alloyohimbine) and 10,308,017 (Gummadiol) showed triple inhibition potential against all the three targets and 102,004,710 (18-Hydroxy-3-epi-alpha-yohimbine) exhibited dual inhibition potential. Hence, the proposed lead molecules from our findings can be further investigated through in vitro and in vivo studies to develop into potential drug candidates against human coronaviral infections.

Dataset Information

Virtual screening and repurposing of FDA approved drugs against COVID-19 main protease.

Aims

Materials and methods

Key findings

Significance

Publications

Virtual screening and repurposing of FDA approved drugs against COVID-19 main protease.

Similar Datasets

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