scholarly journals Targeting the Main Protease of SARS‐CoV‐2: From the Establishment of High Throughput Screening to the Design of Tailored Inhibitors

2021 ◽  
Author(s):  
Julian Breidenbach ◽  
Carina Lemke ◽  
Thanigaimalai Pillaiyar ◽  
Laura Schäkel ◽  
Ghazl Al Hamwi ◽  
...  
Keyword(s):  
High Throughput ◽  
High Throughput Screening ◽  
Main Protease

scholarly journals Targeting the Main Protease of SARS‐CoV‐2: From the Establishment of High Throughput Screening to the Design of Tailored Inhibitors

2021 ◽  
Author(s):  
Julian Breidenbach ◽  
Carina Lemke ◽  
Thanigaimalai Pillaiyar ◽  
Laura Schäkel ◽  
Ghazl Al Hamwi ◽  
...  
Keyword(s):  
High Throughput ◽  
High Throughput Screening ◽  
Main Protease

scholarly journals Therapeutic Drugs Targeting 2019-nCoV Main Protease by High-Throughput Screening

2020 ◽  
Author(s):  
Yan Li ◽  
Jinyong Zhang ◽  
Ning Wang ◽  
Haibo Li ◽  
Yun Shi ◽  
...  
Keyword(s):  
High Throughput ◽  
High Throughput Screening ◽  
Binding Capacity ◽  
Effective Means ◽  
Clinical Applications ◽  
Therapeutic Drugs ◽  
Main Protease ◽  
Novel Coronavirus ◽  
Clinical Drug ◽  
Specific Inhibitors

Abstract2019 Novel Coronavirus (2019-nCoV) is a virus identified as the cause of the outbreak of pneumonia first detected in Wuhan, China. Investigations on the transmissibility, severity, and other features associated with this virus are ongoing. Currently, there is no vaccine or therapeutic antibody to prevent the infection, and more time is required to develop an effective immune strategy against the pathogen. In contrast, specific inhibitors targeting the key protease involved in replication and proliferation of the virus are the most effective means to alleviate the epidemic. The main protease of SARS-CoV is essential for the life cycle of the virus, which showed 96.1% of similarity with the main proteaseof 2019-nCoV, is considered to be an attractive target for drug development. In this study, we have identified 4 small molecular drugs with high binding capacity with SARS-CoV main protease by high-throughput screening based on the 8,000 clinical drug libraries, all these drugs have been widely used in clinical applications with guaranteed safety, which may serve as promising candidates to treat the infection of 2019-nCoV.

scholarly journals High-throughput screening and evaluation of repurposed drugs targeting the SARS-CoV-2 main protease

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Yan Li ◽  
Jinyong Zhang ◽  
Zilei Duan ◽  
Ning Wang ◽  
Xiangcheng Sun ◽  
...  
Keyword(s):  
High Throughput ◽  
High Throughput Screening ◽  
Main Protease ◽  
Repurposed Drugs

scholarly journals Virtual High Throughput Screening Based Prediction of Potential Drugs for COVID-19

2020 ◽  
Author(s):  
Sekhar Talluri
Keyword(s):  
High Throughput ◽  
High Throughput Screening ◽  
Viral Infections ◽  
Genomic Sequence ◽  
Reproduction Number ◽  
Three Dimensional ◽  
Drug Repurposing ◽  
Dimensional Structure ◽  
Main Protease ◽  
Approved Drugs

SARS-CoV-2 is a betacoronavirus that was first identified during the Wuhan COVID-19 epidemic in 2019. It was listed as a potential global health threat by WHO due to high mortality, high basic reproduction number and lack of clinically approved drugs and vaccines for COVID-19. The genomic sequence of the virus responsible for COVID-19, as well as the experimentally determined three dimensional structure of the Main protease (Mpro) are available. The reported structure of the target Mpro was utilized in this study to identify potential drugs for COVID-19 using virtual high throughput screening. The results of this study confirm earlier preliminary reports based on studies of homologs that some of the drugs approved for treatment of other viral infections also have the potential for treatment of COVID-19. Approved anti-viral drugs that target proteases were ranked for potential effectiveness against COVID-19 and novel candidates for drug repurposing were identified.

scholarly journals High-throughput Screening and Experimental Identification of Potent Drugs Targeting SARS-CoV-2 Main Protease

2020 ◽  
Author(s):  
Yan Li ◽  
Jinyong Zhang ◽  
Ning Wang ◽  
Yanjing Zhang ◽  
Yongjun Yang ◽  
...  
Keyword(s):  
High Throughput ◽  
High Throughput Screening ◽  
Drug Targets ◽  
Binding Pocket ◽  
Substrate Binding Pocket ◽  
Stable Conformation ◽  
Cross Docking ◽  
Main Protease ◽  
Computer Based ◽  
Old Drugs

Abstract The main protease (Mpro) is one of the best-characterized drug targets among coronaviruses. In the current study, we adopted a multiple cross-docking strategy against different crystal structures of SARS-CoV-2 Mpro to perform computer-based high-throughput virtual screening of possible inhibitors from a drug database using Autodock Vina and SeeSAR software, combined with our in-house automatic processing scripts. The KDs between screened candidates and Mpro were determined using Biacore. Seven drugs were found to fit the substrate-binding pocket of Mpro with a stable conformation, showing high KDs that ranged from 6.79E-7 M to 5.20E-5 M. Finally, mutagenesis studies confirmed that these drugs interact with Mpro specifically, suggesting that our method was reliable and convincing. Given the safety of these old drugs, they may serve as promising candidates to treat the infection of SARS-CoV-2. Our results also provide rational explanations for the behaviour of five drugs evaluated in clinical trials.

Virtual High Throughput Screening to find suitable inhibitors for SARSCoV-2 Main Protease

2020 ◽  
Vol 18 ◽  
Author(s):  
Upasana Phukan ◽  
Nakul Neog ◽  
Minakshi Puzari ◽  
Mohan Sharma ◽  
Saurov Mahanta ◽  
...  
Keyword(s):  
High Throughput ◽  
Inhibitory Activity ◽  
High Throughput Screening ◽  
Binding Energies ◽  
Health Concern ◽  
Potential Candidate ◽  
Major Health ◽  
Discovery Studio ◽  
Main Protease ◽  
Potential Inhibitors

Background: SARS-CoV-2 virus which originated in Wuhan and quickly spread across various countries has taken the form of a pandemic. It is now a major health concern among everyone and finding a solution to this problem is of utmost importance. Understanding its origin, transmission, and interaction with different compounds is essential to find probable inhibitors. Objective: The objective of our study was to search for potential inhibitors of the main protease of SARS-CoV-2 and to access their drug-like properties. Methodology: In our study, 1909 ligands were filtered through Lipinski filter and ADMET properties along with mutagenic nature were analysed. They were screened for inhibitory activity against the Main Protease of SARS-CoV-2 using BIOVIA Discovery studio. Results: After virtual high throughput screening, two compounds- apigenin and N-(4-bromophenyl)-7-hydroxy-2- iminochromene-3-carboxamide were found to have promising binding energies as well as –CDOCKER energy scores compared to the reported inhibitor. Conclusion: Apigenin seems to be a potential candidate against the main protease of SARS-CoV-2 and must be considered for further experiments.

scholarly journals Identification of SARS-CoV-2 3CL Protease Inhibitors by a Quantitative High-throughput Screening

2020 ◽  
Author(s):  
Wei Zhu ◽  
Miao Xu ◽  
Catherine Z. Chen ◽  
Hui Guo ◽  
Min Shen ◽  
...  
Keyword(s):  
High Throughput ◽  
High Throughput Screening ◽  
Drug Target ◽  
Cytopathic Effect ◽  
Drug Repurposing ◽  
Combination Therapies ◽  
Main Protease ◽  
Investigational Drugs ◽  
3Cl Protease ◽  
Viral Enzyme

AbstractThe outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emphasized the urgency to develop effective therapeutics. Drug repurposing screening is regarded as one of the most practical and rapid approaches for the discovery of such therapeutics. The 3C like protease (3CLpro), or main protease (Mpro) of SARS-CoV-2 is a valid drug target as it is a specific viral enzyme and plays an essential role in viral replication. We performed a quantitative high throughput screening (qHTS) of 10,755 compounds consisting of approved and investigational drugs, and bioactive compounds using a SARS-CoV-2 3CLpro assay. Twenty-three small molecule inhibitors of SARS-CoV-2 3CLpro have been identified with IC50s ranging from 0.26 to 28.85 μM. Walrycin B (IC50 = 0.26 µM), Hydroxocobalamin (IC50 = 3.29 µM), Suramin sodium (IC50 = 6.5 µM), Z-DEVD-FMK (IC50 = 6.81 µM), LLL-12 (IC50 = 9.84 µM), and Z-FA-FMK (IC50 = 11.39 µM) are the most potent 3CLpro inhibitors. The activities of anti-SARS-CoV-2 viral infection was confirmed in 7 of 23 compounds using a SARS-CoV-2 cytopathic effect assay. The results demonstrated a set of SARS-CoV-2 3CLpro inhibitors that may have potential for further clinical evaluation as part of drug combination therapies to treating COVID-19 patients, and as starting points for chemistry optimization for new drug development.

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