scholarly journals Discovery of alliin as a putative inhibitor of the main protease of SARS-CoV-2 by molecular docking

BioTechniques ◽  
2020 ◽  
Vol 69 (2) ◽  
pp. 108-112 ◽  
Author(s):  
Bijun Cheng ◽  
Tianjiao Li
Keyword(s):  
Molecular Docking ◽  
Pharmaceutical Compounds ◽  
The Novel ◽  
Important Target ◽  
Main Protease ◽  
Docking Method ◽  
Life Threatening ◽  
Novel Coronavirus ◽  
Better Than ◽  
Molecular Docking Method

The outbreak of viral pneumonia caused by the novel coronavirus SARS-CoV-2 that began in December 2019 caused high mortality. It has been suggested that the main protease (Mpro) of SARS-CoV-2 may be an important target to discover pharmaceutical compounds for the therapy of this life-threatening disease. Remdesivir, ritonavir and chloroquine have all been reported to play a role in suppressing SARS-CoV-2. Here, we applied a molecular docking method to study the binding stability of these drugs with SARS-CoV-2 Mpro. It appeared that the ligand–protein binding stability of the alliin and SARS-CoV-2 Mpro complex was better than others. The results suggested that alliin may serve as a good candidate as an inhibitor of SARS-CoV-2 Mpro. Therefore, the present research may provide some meaningful guidance for the prevention and treatment of SARS-CoV-2.

Screening of Kabasura Kudineer Chooranam against COVID-19 through Targeting of Main Protease and RNA-Dependent RNA Polymerase of SARS-CoV-2 by Molecular Docking Studies

2020 ◽  
Vol 5 (4) ◽  
pp. 319-331
Author(s):  
K. Gopalasatheeskumar ◽  
Karthikeyen Lakshmanan ◽  
Anguraj Moulishankar ◽  
Jerad Suresh ◽  
D. Kumuthaveni Babu ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Rna Polymerase ◽  
Docking Studies ◽  
The Novel ◽  
Rna Dependent Rna Polymerase ◽  
Molecular Docking Studies ◽  
Main Protease ◽  
Short Span ◽  
Novel Coronavirus

COVID-19 is the infectious pandemic disease caused by the novel coronavirus. The COVID-19 is spread globally in a short span of time. The Ministry of AYUSH, India which promotes Siddha and other Indian system of medicine recommends the use of formulation like Nilavembu Kudineer and Kaba Sura Kudineer Chooranam (KSKC). The present work seeks to provide the evidence for the action of 74 different constituents of the KSKC formulation acting on two critical targets. That is main protease and SARS-CoV-2 RNAdependent RNA polymerase target through molecular docking studies. The molecular docking was done by using AutoDock Tools 1.5.6 of the 74 compounds, about 50 compounds yielded docking results against COVID-19 main protease while 42 compounds yielded against SARSCoV- 2 RNA-dependent RNA polymerase. This research has concluded that the KSKC has the lead molecules that inhibits COVID-19’s target of main protease of COVID-19 and SARS-CoV-2 RNA-dependent RNA polymerase.

scholarly journals Didemnins Inhibit COVID-19 Main Protease (Mpro)

2020 ◽  
Vol 11 (1) ◽  
pp. 8204-8209
Keyword(s):  
Prediction Method ◽  
Target Prediction ◽  
Docking Studies ◽  
Therapeutic Agents ◽  
The Novel ◽  
Main Protease ◽  
Docking Method ◽  
Marine Compounds ◽  
Novel Coronavirus ◽  
Therapeutic Alternatives

The novel coronavirus disease because of infection with the SARS-CoV-2 virus, COVID-19, was first appeared in Wuhan, China, in December 2019. It has spread rapidly all around the World and has been accepted as a pandemic. Specific therapies for COVID-19 treatment is not available for now. Thus, there is a huge effort to develop and discover new therapeutic agents and vaccines by scientists. The design and development of new therapeutic agents for treatment through medicinal chemistry is slow and needed a hard labor process. Thus, it is urgent to achieve the discovery of more effective agents. Marine natural products have antiviral activity and quite significant pharmacological capacity. The antiviral properties of these products are shown as new promising therapeutic alternatives against the viruses. The present work aimed to assess the inhibition potential of Didemnin A, B, and C isolated from tunicates to COVID-19 Mpro protein through a molecular docking method. The molecular characterization of compounds with binding affinity was performed by using the Swiss Target Prediction Method. As a result, the binding energy of Didemnins A, B, and C was calculated as -11.82 kcal/ mol, -10.27 kcal/ mol, and -9.26 kcal/ mol, respectively. Also, the docking studies showed that Didemnin B involved in hydrogen bonding with Glu166 in the active site of the Mpro protein. Therefore, the natural marine compounds have the potential for developing drugs against to SARS-CoV-2 virus, which may aid in overcoming the clinical challenge of the COVID-19 pandemic.

scholarly journals In Silico Screening of Potent Bioactive Compounds from Honey Bee Products Against COVID-19 Target Enzymes

2020 ◽  
Author(s):  
Moataz A. Shaldam ◽  
Galal Yahya ◽  
Nashwa H. Mohamed ◽  
Mohamed M. Abdel-Daim ◽  
Yahya Al Naggar
Keyword(s):  
Molecular Docking ◽  
Honey Bee ◽  
Bioactive Compounds ◽  
Viral Infections ◽  
Good Alternative ◽  
The Novel ◽  
Main Protease ◽  
Novel Coronavirus ◽  
Approved Drugs ◽  
Antiviral Medications

From the early days of the COVID-19 pandemic, side by side to immense investigates to design specific drugs or to develop a potential vaccine for the novel coronavirus. Myriads of FDA approved drugs are massively repurposed for COVID-19 treatment based on molecular docking of selected protein targets that play vital for the replication cycle of the virus. Honey bee products are well known of their nutritional values and medicinal effects. Antimicrobial activity of bee products and natural honey have been documented in several clinical studies and was considered a good alternative for antiviral medications to treat some viral infections. Bee products contain bioactive compounds in the form of a collection of phenolic acids, flavonoids and terpenes of natural origin. We revealed by molecular docking the profound binding affinity of 14 selected phenolics and terpenes present in honey and propolis (bees glue) against the main protease (M<sup>pro</sup>) and RNA dependent RNA polymerase (RdRp) enzymes of the novel 2019-nCoV coronavirus. Of these compounds, <i>p</i>-coumaric acid, ellagic acid, kaemferol and quercetin has the strongest interaction with the 2019-nCoV target enzymes, and they may be considered as an effective 2019-nCoV inhibitors.

Computational drug repurposing study of antiviral drugs against main protease, RNA polymerase, and spike proteins of SARS-CoV-2 using molecular docking method

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Alireza Jalalvand ◽  
Somayeh Behjat Khatouni ◽  
Zahra Bahri Najafi ◽  
Foroozan Fatahinia ◽  
Narges Ismailzadeh ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Rna Polymerase ◽  
3D Structure ◽  
Drug Repurposing ◽  
Antiviral Drugs ◽  
Effective Drug ◽  
Main Protease ◽  
Docking Method ◽  
Inhibitory Potential ◽  
Molecular Docking Method

Abstract Objectives The new Coronavirus (SARS-CoV-2) created a pandemic in the world in late 2019 and early 2020. Unfortunately, despite the increasing prevalence of the disease, there is no effective drug for the treatment. A computational drug repurposing study would be an appropriate and rapid way to provide an effective drug in the treatment of the coronavirus disease of 2019 (COVID-19) pandemic. In this study, the inhibitory potential of more than 50 antiviral drugs on three important proteins of SARS-CoV-2, was investigated using the molecular docking method. Methods By literature review, three important proteins, including main protease, RNA-dependent RNA polymerase (RdRp), and spike, were selected as the drug targets. The three-dimensional (3D) structure of protease, spike, and RdRp proteins was obtained from the Protein Data Bank. Proteins were energy minimized. More than 50 antiviral drugs were considered as candidates for protein inhibition, and their 3D structure was obtained from Drug Bank. Molecular docking settings were defined using Autodock 4.2 software and the algorithm was executed. Results Based on the estimated binding energy of docking and hydrogen bond analysis and the position of drug binding, five drugs including, indinavir, lopinavir, saquinavir, nelfinavir, and remdesivir, had the highest inhibitory potential for all three proteins. Conclusions According to the results, among the mentioned drugs, saquinavir and lopinavir showed the highest inhibitory potential for all three proteins compared to the other drugs. This study suggests that saquinavir and lopinavir could be included in the laboratory phase studies as a two-drug treatment for SARS-CoV-2 inhibition.

scholarly journals In Silico Identification of Potent COVID-19 Main Protease Inhibitors from FDA Approved Antiviral Compounds and Active Phytochemicals through Molecular Docking: A Drug Repurposing Approach

2020 ◽  
Author(s):  
Vaishali Chandel ◽  
Sibi Raj ◽  
Brijesh Rathi ◽  
Dhruv Kumar
Keyword(s):  
Molecular Docking ◽  
Virtual Screening ◽  
Binding Affinity ◽  
Drug Repurposing ◽  
The Novel ◽  
Antiviral Compounds ◽  
Ssrna Virus ◽  
Main Protease ◽  
Adme Properties ◽  
Novel Coronavirus

The Novel Coronavirus (COVID-19) is a positive-sense single-stranded RNA ((+)ssRNA) virus. The COVID-19 Main Proteases play very important role in the propagation of the Novel Coronavirus (COVID-19). It has already killed more than 8000 people around the world and thousands of people are getting infected every day. Therefore, it is very important to identify a potential inhibitor against COVID-19 Main Proteases to inhibit the propagation of the Novel Coronavirus (COVID-19). We have applied a drug repurposing approach of computational methodology, depending on the synergy of molecular docking and virtual screening techniques, aimed to identify possible potent inhibitors against Novel Coronavirus (COVID-19) from FDA approved antiviral compounds and from the library of active phytochemicals. On the basis of recently resolved COVID-19 Main Protease crystal structure (PDB:6LU7), the library of 100 FDA approved antiviral compounds and 1000 active components of Indian Medicinal Plants extracted for screening against COVID-19 Main Protease. The compounds were further screened using Pyrex virtual screening tool and then best inhibitors, top 19 compounds optimally docked to the COVID-19 Main Protease structure to understand the participation of specific amino acids with inhibitors at active sites. Total 19 best compounds were identified after screening based on their highest binding affinity with respect to the other screened compounds. Out of 19, 6 best compounds were further screened based on their binding affinity and best ADME properties. Nelfinavir exhibited highest binding energy -8.4 kcal/mol and strong stability with the TRP207, ILE281, LEU282, PHE3, PHE291, GLN127, ARG4, GLY283, GLU288, LYS5, LYS137, TYR126, GLY138, TYR126, SER139 and VAL135 amino acid residues of COVID-19 Main Protease participating in the interaction at the binding pocket. In addition to Nelfinavir (-8.4), Rhein (-8.1), Withanolide D (-7.8), Withaferin A (-7.7), Enoxacin (-7.4), and Aloe-emodin (-7.4) also showed good binding affinity and best ADME properties. Our findings suggest that these compounds can be used as potential inhibitors against COVID-19 Main Protease, which could be helpful in inhibiting the propagation of the Novel Coronavirus (COVID-19). Moreover, further in vitro and in vivo validation of these findings would be very helpful to bring these inhibitors to next level study.

scholarly journals Therapeutics targeting the main protease of SARS-CoV-2 for the treatment of COVID-19: A molecular modeling approach deciphering relative efficacies

2020 ◽  
Author(s):  
Shuvasish Choudhury ◽  
Purbajyoti Saikia ◽  
Debojyoti Moulick ◽  
Muhammed Khairujjaman Mazumder
Keyword(s):  
Molecular Docking ◽  
Molecular Modeling ◽  
Protease Inhibitors ◽  
Drug Target ◽  
De Novo ◽  
The Novel ◽  
Main Protease ◽  
Docking Tool ◽  
Novel Coronavirus ◽  
Approved Drugs

Abstract The pandemic due to the novel coronavirus 2019, SARS-CoV-2, has led to a global health and economic crisis. The disease, named coronavirus disease (COVID-19), has already affected 3090445 and killed over 217769 people worldwide, as of April 30, 2020. So far, there is no specific effective medicine or vaccine against SARS-CoV-2. Several existing and approved drugs are under clinical studies for re-purposing. However, owing to the emergent situation and thereby to avoid time needed for de novo drug discovery, drug re-purposing remains to be the best option to find an effective therapeutic against the virus. Thus, the preset study was designed to evaluate potency of 82 compound/drugs in inhibiting the main protease (3CLPro) of SARS-CoV-2, using molecular docking tool. This protease is a vital enzyme for replication of the virus, and is thus a promising drug target. The analyzed compounds include 16 known protease inhibitors, two recently suggested α-ketoamides, 24 recently reported putative inhibitors, and 40 phytochemicals. The results indicate that Ritonavir, Indinavir, Montelukast, Nelfinavir, Candoxatril, Tigecycline and Lopinavir to be very potent protease inhibitors. Further, several other drugs and compounds, including phytochemicals, have been identified / predicted to be potent in inhibiting the enzyme. In addition, we hereby report relative efficacies of these compounds in inhibiting 3CLPro. Thus, the present study is significant in the therapeutic intervention of COVID-19.

scholarly journals Exploring the Active Compounds of Traditional Mongolian Medicine in Intervention of Novel Coronavirus (2019-nCoV) Based on Molecular Docking Method

2020 ◽  
Author(s):  
Jiuwang Yu ◽  
Lu Wang ◽  
Lidao Bao
Keyword(s):  
Molecular Docking ◽  
Research And Development ◽  
Molecular Level ◽  
Protein Docking ◽  
Research Strategy ◽  
Docking Method ◽  
Novel Coronavirus ◽  
Potential Inhibitors ◽  
Traditional Mongolian Medicine ◽  
Molecular Docking Method

<p>In this study, a research strategy combining network pharmacological analysis, protein docking and molecular docking virtual computation was adopted. It was found that phillyrin and chlorogenic acid could block the combination of 2019-nCoV S-protein and ACE2 at the molecular level. Both can be used as potential inhibitors of 2019-nCoV for further research and development. </p>

scholarly journals Potential Phytopharmaceutical Constituents of Solanum Trilobatum L. as Significant Inhibitors Against COVID-19: Robust-Binding Mode of Inhibition by Molecular Docking, PASS-Aid Bioactivity and ADMET Investigations

2020 ◽  
Author(s):  
Shanmugam Anandakumar ◽  
Damodharan Kannan ◽  
Eugene Wilson ◽  
Kasthuri Bai Narayanan ◽  
Ganesan Suresh ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Binding Mode ◽  
Therapeutic Drug ◽  
The Novel ◽  
Lipinski’S Rule ◽  
Drug Candidates ◽  
Main Protease ◽  
Solanum Trilobatum ◽  
Novel Coronavirus ◽  
Potential Inhibitors

The novel coronavirus is better known as COVID–19 caused by Severe Acute Respiratory Syndrome Corona–Virus 2 (SARS–CoV–2) which initially outburst at Wuhan in China on December 2019 and spread very rapidly around the globe. Scientists from the global regions endeavours to still probe for detecting potential treatment and discover effective therapeutic drug candidates for this unabated pandemic. In our article, we reported the molecular docking, bioactivity score, ADME and toxicity prediction of the phytoconstituents of <i>Solanum trilobatum</i> Linn. such as Solanidine, Solasodine and <i>a</i>–Solanine as potential inhibitors against the main protease (M<sup>pro</sup>) of SARS–CoV–2 tropism. The molecular docking of Solanidine, Solasodine and a–Solanine has revealed that it bounded deep into the active cavity site on the M<sup>pro</sup>. Further, the pharmacodynamics and bioactivity profile has confirmed that the molecules obeyed the Lipinski’s rule and will be used as notably treasured lead drug candidates to pursue further biochemical and cell–based assays to explore its potential against COVID–19 pandemic. Thus, envisioning thought–provoking research certainly provide new leads for the global researchers.

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