scholarly journals Repurposing of Anthelmintic Drugs against SARS-CoV-2 (Mpro and RdRp): Novel Disease, Older Therapeutics

2020 ◽  
Vol 10 (2) ◽  
pp. 2331-2338
Keyword(s):  
Antiviral Activity ◽  
Protease Inhibitor ◽  
In Silico ◽  
Rna Polymerases ◽  
The Novel ◽  
Inhibitor Activity ◽  
Main Protease ◽  
Promising Target ◽  
Potential Inhibitors ◽  
Anthelmintic Drugs

Since late December 2019, the entire nations are facing the novel enemy of COVID-19, which has imposed a tremendous burden on the researchers across the globe to develop a treatment for it. Recognition of main protease and RNA dependent RNA polymerases as a promising target of SARS-CoV-2 encouraged us to repurpose some older antihelmintic drugs against COVID-19. In this constructive research, we have investigated anthelmintic drugs' antiviral activity, including ivermectin, doramectin, and selamectin, for their antiviral potential against SARS-CoV-2 by employing in silico tools. The selected drugs, including ivermectin, doramectin, and selamectin, were encountered as potential inhibitors of SARS-CoV-2 RNA-dependent RNA polymerases with an affinity of -9.2, -10.0, and -10.2 kcal/mol. They were found to exhibit main protease inhibitor activity with an affinity of -8.3, -8.7, and -9.0, respectively. Thus, using the repurposing approach in conjugation within silico tools, we have proposed ivermectin, doramectin, and selamectin as potential antivirals against SARS-CoV-2.

scholarly journals Recognition of Natural Products as Potential Inhibitors of COVID-19 Main Protease (Mpro): In-Silico Evidences

2020 ◽  
Vol 10 (5) ◽  
pp. 297-306 ◽  
Author(s):  
Rohan R. Narkhede ◽  
Ashwini V. Pise ◽  
Rameshwar S. Cheke ◽  
Sachin D. Shinde
Keyword(s):  
Natural Products ◽  
Molecular Docking ◽  
Antiviral Activity ◽  
Drug Development ◽  
In Silico ◽  
Herbal Remedies ◽  
Active Compounds ◽  
Main Protease ◽  
Future Drug ◽  
Potential Inhibitors

Abstract SARS-CoV-2 (2019-nCoV) emerged in 2019 and proliferated rapidly across the globe. Scientists are attempting to investigate antivirals specific to COVID-19 treatment. The 2019-nCoV and SARS-CoV utilize the same receptor of the host which is COVID-19 of the main protease (Mpro).COVID-19 caused by SARS-CoV-2 is burdensome to overcome by presently acquired antiviral candidates. So the objective and purpose of this work was to investigate the plants with reported potential antiviral activity. With the aid of in silico techniques such as molecular docking and druggability studies, we have proposed several natural active compounds including glycyrrhizin, bicylogermecrene, tryptanthrine, β-sitosterol, indirubin, indican, indigo, hesperetin, crysophanic acid, rhein, berberine and β-caryophyllene which can be encountered as potential herbal candidate exhibiting anti-viral activity against SARS-CoV-2. Promising docking outcomes have been executed which evidenced the worthy of these selected herbal remedies for future drug development to combat coronavirus disease. Graphic Abstract

scholarly journals In silico investigation of potential inhibitors to main protease and spike protein of SARS-CoV-2 in propolis

2021 ◽  
pp. 100969
Author(s):  
Azza H. Harisna ◽  
Rizky Nurdiansyah ◽  
Putri H. Syaifie ◽  
Dwi W. Nugroho ◽  
Kurniawan E. Saputro ◽  
...  
Keyword(s):  
In Silico ◽  
Spike Protein ◽  
Main Protease ◽  
Potential Inhibitors

scholarly journals An Integrative in Silico Drug Repurposing Approach for Identification of Potential Inhibitors of SARS‐CoV‐2 Main Protease

2021 ◽  
Author(s):  
Nemanja Djokovic ◽  
Dusan Ruzic ◽  
Teodora Djikic ◽  
Sandra Cvijic ◽  
Jelisaveta Ignjatovic ◽  
...  
Keyword(s):  
In Silico ◽  
Drug Repurposing ◽  
Main Protease ◽  
Potential Inhibitors

In silico screening of phytoconstituents with antiviral activities against SARS-COV-2 main protease, Nsp12 polymerase and Nsp13 helicase proteins

2021 ◽  
Vol 18 ◽  
Author(s):  
Jainey James ◽  
Divya Jyothi ◽  
Sneh Priya
Keyword(s):  
Antiviral Activity ◽  
Molecular Interactions ◽  
In Silico ◽  
Antiviral Treatment ◽  
In Vivo Studies ◽  
Main Protease ◽  
Hypothesis Model ◽  
Antiviral Activities ◽  
Pharmacophore Hypothesis

Aims: The present study aim was to analyse the molecular interactions of the phytoconstituents known for their antiviral activity with the SARS-CoV-2 nonstructural proteins such as main protease (6LU7), Nsp12 polymerase (6M71), and Nsp13 helicase (6JYT). The applied in silico methodologies was molecular docking and pharmacophore modeling using Schrodinger software. Methods: The phytoconstituents were taken from PubChem, and SARS-CoV-2 proteins were downloaded from the protein data bank. The molecular interactions, binding energy, ADMET properties and pharmacophoric features were analysed by glide XP, prime MM-GBSA, qikprop and phase application of Schrodinger respectively. The antiviral activity of the selected phytoconstituents was carried out by PASS predictor, online tools. Results: The docking score analysis showed that quercetin 3-rhamnoside (-8.77 kcal/mol) and quercetin 3-rhamnoside (-7.89 kcal/mol) as excellent products to bind with their respective targets such as 6LU7, 6M71 and 6JYT. The generated pharmacophore hypothesis model validated the docking results, confirming the hydrogen bonding interactions of the amino acids. The PASS online tool predicted constituent's antiviral potentials. Conclusion: The docked phytoconstituents showed excellent interactions with the SARS-CoV-2 proteins, and on the outset, quercetin 3-rhamnoside and quercetin 7-rhamnoside have well-interacted with all the three proteins, and these belong to the plant Houttuynia cordata. The pharmacophore hypothesis has revealed the characteristic features responsible for their interactions, and PASS prediction data has supported their antiviral activities. Thus, these natural compounds could be developed as lead molecules for antiviral treatment against SARS-CoV-2. Further in-vitro and in-vivo studies could be carried out to provide better drug therapy.

scholarly journals Quinoline and Quinazoline Alkaloids against COVID-19: An In Silico Multitarget Approach

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Esraa M. O. A. Ismail ◽  
Shaza W. Shantier ◽  
Mona S. Mohammed ◽  
Hassan H. Musa ◽  
Wadah Osman ◽  
...  
Keyword(s):  
Antimalarial Activity ◽  
The Novel ◽  
Socioeconomic Impacts ◽  
Health Crisis ◽  
Natural Sources ◽  
Angiotensin Converting Enzyme 2 ◽  
Main Protease ◽  
Recent Outbreak ◽  
Novel Coronavirus ◽  
Potential Inhibitors

The recent outbreak of the highly contagious coronavirus disease 2019 (COVID-19) caused by the novel coronavirus SARS-CoV-2 has created a global health crisis with socioeconomic impacts. Although, recently, vaccines have been approved for the prevention of COVID-19, there is still an urgent need for the discovery of more efficacious and safer drugs especially from natural sources. In this study, a number of quinoline and quinazoline alkaloids with antiviral and/or antimalarial activity were virtually screened against three potential targets for the development of drugs against COVID-19. Among seventy-one tested compounds, twenty-three were selected for molecular docking based on their pharmacokinetic and toxicity profiles. The results identified a number of potential inhibitors. Three of them, namely, norquinadoline A, deoxytryptoquivaline, and deoxynortryptoquivaline, showed strong binding to the three targets, SARS-CoV-2 main protease, spike glycoprotein, and human angiotensin-converting enzyme 2. These alkaloids therefore have promise for being further investigated as possible multitarget drugs against COVID-19.

scholarly journals ACTIVITY SCREENING AND STRUCTURE MODIFICATION OF ARTOCARPIN AGAINST ACE2 AND MAIN PROTEASE THROUGH IN SILICO METHOD

2021 ◽  
pp. 192-198
Author(s):  
MUHAMMAD FAUZI ◽  
ARIS FADILLAH ◽  
FAUZI RAHMAN ◽  
JUWITA RAMADHANI ◽  
KARINA ERLIANTI ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
In Silico ◽  
Docking Simulation ◽  
Positive Control ◽  
Hydroxyl Group ◽  
Artocarpus Altilis ◽  
Main Protease ◽  
Activity Screening ◽  
The Stability ◽  
The Right

Objective: SARS-CoV-2 is a type of coronavirus that causes COVID-19 disease. Currently, the right and effective drug for the treatment of COVID-19 has not been found. Artocarpin in the breadfruit plant (Artocarpus altilis), which was tested, has been shown to have antiviral activity. However, artocarpin has a hydroxyl group that can undergo oxidation within a certain time, thereby reducing the stability of the compound and non-specific antiviral activity. Methods: In this study, the structural modification of artocarpin was carried out to obtain compounds with anticoronavirus activity with good physicochemical properties. This research was conducted in silico, including molecular docking simulation, bioavailability prediction, and preADMET. Results: The top 20 modified compounds were selected from each target's top 3 compounds, which had better bond energies compared to the positive control. These 3 compounds have the potential to inhibit ACE2 and Mpro receptors and 1 compound are better at inhibiting both. Conclusion: From the results of the research conducted, we conclude that the 3 best compounds can be potential candidates that can be developed as COVID-19 therapy.

scholarly journals Repurposing of FDA Approved Drugs for the Identification of Potential Inhibitors of SARS-CoV-2 Main Protease

2020 ◽  
Author(s):  
Abhik Kumar Ray ◽  
Parth Sarthi Sen Gupta ◽  
Saroj Kumar Panda ◽  
Satyaranjan Biswal ◽  
Malay Kumar Rana
Keyword(s):  
Virtual Screening ◽  
Binding Energies ◽  
Great Promise ◽  
Main Protease ◽  
Promising Target ◽  
Inhibitory Potential ◽  
Novel Coronavirus ◽  
Approved Drugs ◽  
Potential Inhibitors ◽  
Fda Approved Drugs

<p>COVID-19, responsible for several deaths, demands a cumulative effort of scientists worldwide to curb the pandemic. The main protease, responsible for the cleavage of the polyprotein and formation of replication complex in virus, is considered as a promising target for the development of potential inhibitors to treat the novel coronavirus. The effectiveness of FDA approved drugs targeting the main protease in previous SARS-COV (s) reported earlier indicates the chances of success for the repurposing of FDA drugs against SARS-COV-2. Therefore, in this study, molecular docking and virtual screening of FDA approved drugs, primarily of three categories: antiviral, antimalarial, and peptide, are carried out to investigate their inhibitory potential against the main protease. Virtual screening has identified 53 FDA drugs on the basis of their binding energies (< -7.0 kcal/mol), out of which the top two drugs Velpatasvir (-9.1 kcal/mol) and Glecaprevir (-9.0 kcal/mol) seem to have great promise. These drugs have a stronger affinity to the SARS-CoV-2 main protease than the crystal bound inhibitor α-ketoamide 13B (-6.7 kcal/mol) or Indinavir (-7.5 kcal/mol) that has been proposed in a recent study as one of the best drugs for SARS-CoV-2. The <i>in-silico</i> efficacies of the screened drugs could be instructive for further biochemical and structural investigation for repurposing. The molecular dynamics studies on the shortlisted drugs are underway. </p>

scholarly journals The dolabellane diterpenes as potential inhibitors of the SARS-CoV-2 main protease: molecular insight of the inhibitory mechanism through computational studies

RSC Advances ◽  
2021 ◽  
Vol 11 (62) ◽  
pp. 39455-39466
Author(s):  
Nanik Siti Aminah ◽  
Muhammad Ikhlas Abdjan ◽  
Andika Pramudya Wardana ◽  
Alfinda Novi Kristanti ◽  
Imam Siswanto ◽  
...  
Keyword(s):  
In Silico ◽  
Computational Studies ◽  
Inhibitory Mechanism ◽  
Main Protease ◽  
Potential Inhibitors

An investigation on dolabellane derivatives to understand their potential in inhibiting the SARS-CoV-2 main protease (3CLpro) using an in silico approach.

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