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Proteomics advances towards developing SARS-CoV-2 therapeutics using in silico drug repurposing approaches.

ABSTRACT: Standing amidst the COVID-19 pandemic, we have faced major medical and economic crisis in recent times which remains to be an unresolved issue till date. Although the scientific community has made significant progress towards diagnosis and understanding the disease; however, effective therapeutics are still lacking. Several omics-based studies, especially proteomics and interactomics, have contributed significantly in terms of identifying biomarker panels that can potentially be used for the disease prognosis. This has also paved the way to identify the targets for drug repurposing as a therapeutic alternative. US Food and Drug Administration (FDA) has set in motion more than 500 drug development programs on an emergency basis, most of them are focusing on repurposed drugs. Remdesivir is one such success of a robust and quick drug repurposing approach. The advancements in omics-based technologies has allowed to explore altered host proteins, which were earlier restricted to only SARS-CoV-2 protein signatures. In this article, we have reviewed major contributions of proteomics and interactomics techniques towards identifying therapeutic targets for COVID-19. Furthermore, in-silico molecular docking approaches to streamline potential drug candidates are also discussed.

SUBMITTER: Mukherjee A

PROVIDER: S-EPMC8222565 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Proteomics advances towards developing SARS-CoV-2 therapeutics using in silico drug repurposing approaches.

Mukherjee Amrita A Verma Ayushi A Bihani Surbhi S Burli Ananya A Mantri Krishi K Srivastava Sanjeeva S

Drug discovery today. Technologies 20210624

Standing amidst the COVID-19 pandemic, we have faced major medical and economic crisis in recent times which remains to be an unresolved issue till date. Although the scientific community has made significant progress towards diagnosis and understanding the disease; however, effective therapeutics are still lacking. Several omics-based studies, especially proteomics and interactomics, have contributed significantly in terms of identifying biomarker panels that can potentially be used for the dis ...[more]

PMID: 34906319

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Project description:The pandemic of coronavirus disease 2019 (COVID-19) caused by the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a significant impact on the economy and public health worldwide. Therapeutic options such as drugs and vaccines for this newly emerged disease are eagerly desired due to the high mortality. Using the U.S. Food and Drug Administration (FDA) approved drugs to treat a new disease or entirely different diseases, in terms of drug repurposing, minimizes the time and cost of drug development compared to the de novo design of a new drug. Drug repurposing also has some other advantages such as reducing safety evaluation to accelerate drug application on time. Carvedilol, a non-selective beta-adrenergic blocker originally designed to treat high blood pressure and manage heart disease, has been shown to impact SARS-CoV-2 infection in clinical observation and basic studies. Here, we applied computer-aided approaches to investigate the possibility of repurposing carvedilol to combat SARS-CoV-2 infection. The molecular mechanisms and potential molecular targets of carvedilol were identified by evaluating the interactions of carvedilol with viral proteins. Additionally, the binding affinities of in vivo metabolites of carvedilol with selected targets were evaluated. The docking scores for carvedilol and its metabolites with RdRp were - 10.0 kcal/mol, - 9.8 kcal/mol (1-hydroxyl carvedilol), - 9.7 kcal/mol (3-hydroxyl carvedilol), - 9.8 kcal/mol (4-hydroxyl carvedilol), - 9.7 kcal/mol (5-hydroxyl carvedilol), - 10.0 kcal/mol (8-hydroxyl carvedilol), and - 10.1 kcal/mol (O-desmethyl carvedilol), respectively. Using the molecular dynamics simulation (100 ns) method, we further confirmed the stability of formed complexes of RNA-dependent RNA polymerase (RdRp) and carvedilol or its metabolites. Finally, the drug-target interaction mechanisms that contribute to the complex were investigated. Overall, this study provides the molecular targets and mechanisms of carvedilol and its metabolites as repurposed drugs to fight against SARS-CoV-2 infection.

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Proteomics advances towards developing SARS-CoV-2 therapeutics using in silico drug repurposing approaches.

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Proteomics advances towards developing SARS-CoV-2 therapeutics using in silico drug repurposing approaches.

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