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 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 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 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.

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 Potential of Plant Bioactive Compounds as SARS-CoV-2 Main Protease (Mpro) and Spike (S) Glycoprotein Inhibitors: A Molecular Docking Study

2020 ◽  
Author(s):  
Trina Ekawati Tallei ◽  
Sefren Geiner Tumilaar ◽  
Nurdjannah Jane Niode ◽  
Fatimawali Fatimawali ◽  
Billy Johnson Kepel ◽  
...  
Keyword(s):  
Free Energy ◽  
Molecular Docking ◽  
Bioactive Compounds ◽  
Binding Free Energy ◽  
Epigallocatechin Gallate ◽  
Docking Study ◽  
Molecular Docking Study ◽  
Ligand Complex ◽  
Main Protease ◽  
Glycoprotein Inhibitors

Since the outbreak of the COVID-19 (Coronavirus Disease 19) pandemic, researchers have been trying to investigate several active compounds found in plants that have the potential to inhibit the proliferation of SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2). The present study aimed to evaluate bioactive compounds found in plants by using a molecular docking approach to inhibit the Main Protease (Mpro) and Spike (S) glycoprotein of SARS-CoV-2. The evaluation was performed on the docking scores calculated using AutoDock Vina as a docking engine. A rule of five (RO5) was calculated to determine whether a compound meets the criteria as an active drug orally in humans. The determination of the docking score was done by selecting the best conformation of the protein-ligand complex that had the highest affinity (most negative Gibbs' free energy of binding / &Delta;G). As a comparison, nelfinavir (an antiretroviral drug), chloroquine and hydroxychloroquine sulfate (anti-malarial drugs recommended by the FDA as emergency drugs) were used. The results showed that hesperidin, nabiximols, pectolinarin, epigallocatechin gallate, and rhoifolin had better poses than nelfinavir, chloroquine, and hydroxychloroquine sulfate as spike glycoprotein inhibitors. Hesperidin, rhoifolin, pectolinarin, and nabiximols had about the same pose as nelfinavir, but were better than chloroquine and hydroxychloroquine sulfate as Mpro inhibitors. These plant compounds have the potential to be developed as specific therapeutic agents against COVID-19. Several natural compounds of plants evaluated in this study showed better binding free energy compared to nelfinavir, chloroquine, and hydroxychloroquine sulfate which so far are recommended in the treatment of COVID-19. As judged by the RO5 and previous study by others, the compounds kaempferol, herbacetin, eugenol, and 6-shogaol have good oral bioavailability, so they are also seen as promising candidates for the development lead compounds to treat infections caused by SARS-CoV-2.

scholarly journals Molecular docking identification of plant-derived inhibitors of the COVID-19 main protease

2021 ◽  
Vol 103 (3) ◽  
pp. 37-46
Author(s):  
S.S. Bhujbal ◽  
◽  
M. Kale ◽  
B. Chawale ◽  
◽  
...  
Keyword(s):  
Bioactive Compounds ◽  
Drug Target ◽  
Viral Proteins ◽  
Natural Compounds ◽  
Therapeutic Agents ◽  
High Rate ◽  
Therapeutic Drug ◽  
Research Organizations ◽  
Main Protease ◽  
Modeling Techniques

COVID-19 cases increase at a high rate and become dangerous in recent months. As a consequence, some healthcare and research organizations are attempting to find an effective cure for the COVID-19 outbreak. Many natural products have been reported to have powerful activity against COVID-19 in recent research studies. The primary aim of this article is to establish natural bioactive compounds with suitable antiviral properties. Lui et al. have reported in their study that SARS-Cov-2 main protease is present in a crystalline structure known as a novel therapeutic drug target. It is important to inhibit SARS-Cov-2 main protease to stop the replication of viral proteins. In this study natural compounds were screened using molecular modeling techniques to investigate probable bioactive compounds that block SARS-Cov-2. From these studies many natural compounds were found to have the potential to interact with viral proteins and show inhibitory activity against COVID-19 main protease (Mpro) and these natural compounds were also compared to known antiviral drugs such as Saquinavir and Remdesivir. Besides that, additional research is needed before these potential leads can be developed into natural therapeutic agents against COVID-19 to fight the epidemic.

scholarly journals Discovery of Fungal Metabolites Bergenin, Quercitrin and Dihydroartemisinin as Potential Inhibitors Against Main Protease of SARS-CoV-2

2020 ◽  
Author(s):  
Ravi Patel ◽  
Akash Vanzara ◽  
Nimisha Patel ◽  
Ajit Vasava ◽  
Sachin Patil ◽  
...  
Keyword(s):  
Bioactive Compounds ◽  
Active Site ◽  
Electrostatic Interactions ◽  
Hydrophobic Interactions ◽  
Binding Energies ◽  
Crystallographic Structure ◽  
Medicinal Uses ◽  
Main Protease ◽  
Cyathus Stercoreus ◽  
Potential Inhibitors

Emergence of severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) infection has given rise to COVID-19 pandemic, that is wreaking havoc worldwide. Therefore, there is an urgent need to find out novel drugs to combat SARS-CoV-2 infection. In this backdrop, the present study was aimed to assess potent bioactive compounds from different fungi as potential inhibitors of SARS-CoV-2 main protease (M<sup>pro</sup>) using an <i>in-silico</i> analysis. Nearly 118 bioactive compounds were extracted from <i>Dictyophora indusiata</i>, <i>Geassstrum triplex</i> and <i>Cyathus stercoreus </i>and identified using HR LC/MS analysis. Of which, only bergenin (<i>D. indusiata</i>), quercitrin (<i>G. triplex</i>) and dihydroartemisinin (<i>C. stercoreus</i>) were selected based on their medicinal uses, binding score and active site covered. The 6LU7, a protein crystallographic structure of SARS-CoV-2 M<sup>pro</sup>, was docked with bergenin, quercitrin and dihydroartemisinin using Autodock 4.2 and the binding energies obtained were -7.86, -10.29 and -7.20 kcal/mol, respectively. Bergenin, quercitrin and dihydroartemisinin formed hydrogen bond, electrostatic interactions and hydrophobic interactions with foremost active site amino acids THR190, GLU166, GLN189, GLY143, HIS163, HIS164, CYS145 and PHE140. Present investigation suggests that these three drugs may be used as alternative inhibitors against SARS-CoV-2 M<sup>pro</sup>. However, further research is necessary to assess <i>in vitro</i> potential of these drugs. To the best of our knowledge, present investigation reported these three bioactive compounds of fungal origin for the first time.

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
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