scholarly journals Revisiting activity of some glucocorticoids as a potential inhibitor of SARS-CoV-2 main protease: theoretical study

RSC Advances ◽  
2021 ◽  
Vol 11 (17) ◽  
pp. 10027-10042 ◽  
Author(s):  
Ayman Abo Elmaaty ◽  
Radwan Alnajjar ◽  
Mohammed I. A. Hamed ◽  
Muhammad Khattab ◽  
Mohamed M. Khalifa ◽  
...  
Keyword(s):  
Theoretical Study ◽  
Death Toll ◽  
Potential Inhibitor ◽  
Main Protease ◽  
Novel Drugs

The global breakout of COVID-19 and raised death toll has prompted scientists to develop novel drugs capable of inhibiting SARS-CoV-2.

scholarly journals Toward the Identification of Potential α-Ketoamide Covalent Inhibitors for SARS-CoV-2 Main Protease: Fragment-Based Drug Design and MM-PBSA Calculations

Processes ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 1004
Author(s):  
Mahmoud A. El Hassab ◽  
Mohamed Fares ◽  
Mohammed K. Abdel-Hamid Amin ◽  
Sara T. Al-Rashood ◽  
Amal Alharbi ◽  
...  
Keyword(s):  
Drug Design ◽  
Active Site ◽  
Binding Free Energy ◽  
Stable Complex ◽  
Active Site Residues ◽  
Structure Based Drug Design ◽  
Enzyme Active Site ◽  
Potential Inhibitor ◽  
Main Protease ◽  
Covalent Docking

Since December 2019, the world has been facing the outbreak of the SARS-CoV-2 pandemic that has infected more than 149 million and killed 3.1 million people by 27 April 2021, according to WHO statistics. Safety measures and precautions taken by many countries seem insufficient, especially with no specific approved drugs against the virus. This has created an urgent need to fast track the development of new medication against the virus in order to alleviate the problem and meet public expectations. The SARS-CoV-2 3CL main protease (Mpro) is one of the most attractive targets in the virus life cycle, which is responsible for the processing of the viral polyprotein and is a key for the ribosomal translation of the SARS-CoV-2 genome. In this work, we targeted this enzyme through a structure-based drug design (SBDD) protocol, which aimed at the design of a new potential inhibitor for Mpro. The protocol involves three major steps: fragment-based drug design (FBDD), covalent docking and molecular dynamics (MD) simulation with the calculation of the designed molecule binding free energy at a high level of theory. The FBDD step identified five molecular fragments, which were linked via a suitable carbon linker, to construct our designed compound RMH148. The mode of binding and initial interactions between RMH148 and the enzyme active site was established in the second step of our protocol via covalent docking. The final step involved the use of MD simulations to test for the stability of the docked RMH148 into the Mpro active site and included precise calculations for potential interactions with active site residues and binding free energies. The results introduced RMH148 as a potential inhibitor for the SARS-CoV-2 Mpro enzyme, which was able to achieve various interactions with the enzyme and forms a highly stable complex at the active site even better than the co-crystalized reference.

scholarly journals Azadirachtin-A a bioactive compound from Azadiracta indica is a potential inhibitor of SARS-CoV-2 main protease

2021 ◽  
Vol 01 (01) ◽  
pp. 01-08
Author(s):  
Eustace Berinyuy ◽  
◽  
Jonathan Ibrahim ◽  
Blessing Alozieuwa
Keyword(s):  
Bioactive Compound ◽  
Docking Study ◽  
Preclinical Study ◽  
Binding Modes ◽  
Molecular Docking Study ◽  
Potential Inhibitor ◽  
Main Protease ◽  
Binding Cavity ◽  
Approved Drugs ◽  
Azadirachtin A

Despite the growing scientific interest in finding effective treatment, SARS-CoV-2 virus remains a global major health burden and public health emergency. SARS-CoV main protease (Mpro) also known as chymotrypsin-like protease (3CLpro) is an important protein identified to be vital for SARS-CoV-2 survival. However, to date, there are no clinically approved drugs or antibodies specific for SARS-CoV-2. In the present study, we evaluated the interaction of 3CLpro with azadirachtin-A a bioactive compound from Azadiracta indica using in silico molecular docking study. Our results revealed that Azadiractin A docked well into the binding cavity of 3CLproSARS-CoV-2 with binding affinities ranges between -6.3 and -5.20 kcal/mol, and Pkd of 5.82~6.10 for the ten best binding modes. Azadiractin interacted with the active site of 3CLpro-SARS-CoV-2 by 2 conventional hydrogen bonding to HIS163 and GLU166, C-H interactions with HIS127, and alkyl interaction with PRO168 of the 3CLpro-SARS-CoV-2. We also found that the Azadiractin-A_3CLpro-SARS-CoV-2 complex is stabilized by various Vander wall forces with ASN142, LEU141, PHE140, MET165, GLN189, LEU167, THR190, and ALA191. In conclusion, our results suggested that Azadirachtin-A could be a potential inhibitor of SARS-CoV-2 main protease, thus worthy of further preclinical study.

Novel Drugs Targeting the SARS-CoV-2/COVID-19 Machinery

2020 ◽  
Vol 20 (16) ◽  
pp. 1423-1433 ◽  
Author(s):  
Ariane Sternberg ◽  
Dwight L. McKee ◽  
Cord Naujokat
Keyword(s):  
Host Cell ◽  
Protein Processing ◽  
Cell Entry ◽  
Genome Replication ◽  
Rna Dependent Rna Polymerase ◽  
Main Protease ◽  
Novel Drugs ◽  
Pathogenic Viruses ◽  
Repurposed Drugs ◽  
Host Cell Entry

Like other human pathogenic viruses, coronavirus SARS-CoV-2 employs sophisticated macromolecular machines for viral host cell entry, genome replication and protein processing. Such machinery encompasses SARS-CoV-2 envelope spike (S) glycoprotein required for host cell entry by binding to the ACE2 receptor, viral RNA-dependent RNA polymerase (RdRp) and 3-chymotrypsin-like main protease (3Clpro/Mpro). Under the pressure of the accelerating COVID-19 pandemic caused by the outbreak of SARS-CoV-2 in Wuhan, China in December 2019, novel and repurposed drugs were recently designed and identified for targeting the SARS-CoV-2 reproduction machinery, with the aim to limit the spread of SARS-CoV-2 and morbidity and mortality due to the COVID-19 pandemic.

scholarly journals MOLECULAR DOCKING STUDY TO IDENTIFY POTENTIAL INHIBITOR OF COVID-19 MAIN PROTEASE ENZYME: AN IN-SILICO APPROACH

2020 ◽  
Author(s):  
Anurag Agrawal ◽  
Nem Kumar Jain ◽  
Neeraj Kumar ◽  
Giriraj T Kulkarni
Keyword(s):  
Molecular Docking ◽  
Active Site ◽  
Docking Study ◽  
Molecular Docking Study ◽  
Potential Threat ◽  
Discovery Studio ◽  
Chemical Structures ◽  
Potential Inhibitor ◽  
Protease Enzyme ◽  
Main Protease

This study belongs to identification of suitable COVID-19 inhibitors<br><div><br></div><div>Coronavirus became pandemic very soon and is a potential threat to human lives across the globe. No approved drug is currently available therefore an urgent need has been developed for any antiviral therapy for COVID-19. For the molecular docking study, ten herbal molecules have been included in the current study. The three-dimensional chemical structures of molecules were prepared through ChemSketch 2015 freeware. Molecular docking study was performed using AutoDock 4.2 simulator and Discovery studio 4.5 was employed to predict the active site of target enzyme. Result indicated that all-natural molecules found in the active site of enzyme after molecular docking. Oxyacanthine and Hypericin (-10.990 and -9.05 and kcal/mol respectively) have shown good binding efficacy among others but Oxyacanthine was the only natural product which made some of necessary interactions with residues in the enzyme require for target inhibition. Therefore Oxyacanthine may be considered to be potential inhibitor of main protease enzyme of virus but need to be explored for further drug development process. <br></div>

scholarly journals Andrographolide as a potential inhibitor of SARS-CoV-2 main protease: an in silico approach

2020 ◽  
pp. 1-7 ◽  
Author(s):  
Sukanth Kumar Enmozhi ◽  
Kavitha Raja ◽  
Irudhayasamy Sebastine ◽  
Jerrine Joseph
Keyword(s):  
In Silico ◽  
Potential Inhibitor ◽  
Main Protease

scholarly journals Employing bioactive compounds derived from Ipomoea obscura (L.) to evaluate potential inhibitor for SARS‐CoV‐2 main protease and ACE2 protein

2020 ◽  
Vol 1 (2) ◽  
pp. 168-179
Author(s):  
Saravana Prabha Poochi ◽  
Murugesh Easwaran ◽  
Balamuralikrishnan Balasubramanian ◽  
Mohan Anbuselvam ◽  
Arun Meyyazhagan ◽  
...  
Keyword(s):  
Bioactive Compounds ◽  
Potential Inhibitor ◽  
Main Protease ◽  
Ipomoea Obscura

scholarly journals Computational Screening for Potential Drug Candidates Against SARS-CoV-2 Main Protease

2020 ◽  
Author(s):  
Bruno Andrade ◽  
Preetam Ghosh ◽  
Debmalya Barth ◽  
Sandeep Tiwari ◽  
Raner José Santana Silva ◽  
...  
Keyword(s):  
Potential Drug ◽  
Drug Candidates ◽  
Positive Effects ◽  
Computational Screening ◽  
Main Protease ◽  
Zinc Database ◽  
Novel Drugs ◽  
Structural Assembly

Background: SARS-CoV-2 that are the causal agent of a current pandemic are enveloped, positive-sense, single-stranded RNA viruses of the Coronaviridae family. Proteases of SARS-CoV-2 are necessary for viral replication, structural assembly and pathogenicity. The ~33.8KDa Mpro protease of SARS-CoV-2 is a non-human homologue and highly conserved among several coronaviruses indicating Mpro could be a potential drug target for Coronaviruses.Methods: Here we performed computational ligand screening of four pharmacophores (OEW, Remdesivir, Hydroxycholoquine and N3) that are presumed to have positive effects against SARS-CoV-2 Mpro protease (6LU7) and also screened 50,000 molecules from the ZINC Database dataset against this protease target.Results: We found 40 pharmacophore-like structures of natural compounds from diverse chemical classes that exhibited better affinity of docking as compared to the known ligands. The 10 best selected ligands namely, ZINC1845382, ZINC1875405, ZINC2092396, ZINC2104424, ZINC44018332, ZINC2101723, ZINC2094526, ZINC2094304, ZINC2104482, ZINC3984030, and ZINC1531664, are mainly classified as &beta;-carboline, Alkaloids and Polyflavonoids, and all of them displayed interactions with dyad CYS145 and HIS41 from the protease pocket in a similar way as with other known ligands.Conclusion: Our results suggest that these 10 molecules could be effective against SARS-CoV-2 protease and may be tested in vitro and in vivo to develop novel drugs against this virus.

scholarly journals Nelfinavir was predicted to be a potential inhibitor of 2019-nCov main protease by an integrative approach combining homology modelling, molecular docking and binding free energy calculation

2020 ◽  
Author(s):  
Zhijian Xu ◽  
Cheng Peng ◽  
Yulong Shi ◽  
Zhengdan Zhu ◽  
Kaijie Mu ◽  
...  
Keyword(s):  
Free Energy ◽  
Binding Free Energy ◽  
Homology Modelling ◽  
Binding Mode ◽  
Free Energy Calculations ◽  
Integrative Approach ◽  
Energy Calculation ◽  
Potential Inhibitor ◽  
Small Molecule Drugs ◽  
Main Protease

Abstract2019-nCov has caused more than 80 deaths as of 27 January 2020 in China, and infection cases have been reported in more than 10 countries. However, there is no approved drug to treat the disease. 2019-nCov Mpro is a potential drug target to combat the virus. We built homology models based on SARS Mpro structures, and docked 1903 small molecule drugs to the models. Based on the docking score and the 3D similarity of the binding mode to the known Mpro ligands, 4 drugs were selected for binding free energy calculations. Both MM/GBSA and SIE methods voted for nelfinavir, with the binding free energy of −24.69±0.52 kcal/mol and −9.42±0.04 kcal/mol, respectively. Therefore, we suggested that nelfinavir might be a potential inhibitor against 2019-nCov Mpro.

Evaluation of RevX Solution Extract as a Potential Inhibitor of the Main Protease of SARS-CoV-2— In Vitro Study and Molecular Docking

2021 ◽  
Author(s):  
Tung-Kung Wu ◽  
Feng-Pai Chou ◽  
Chia-Chun Liu ◽  
Giang Nguyet Huong Huynh ◽  
Hsiu-Fu Hsu ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Potential Inhibitor ◽  
Main Protease
Sign in / Sign up

Export Citation Format

Share Document