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 Computational Modeling Indicates A Decreased Affinity of SARS-CoV-2 to ACE2 by Steroids

2020 ◽  
Author(s):  
Alireza Mansouri ◽  
Rasoul Kowsar ◽  
Khaled Sadeghi ◽  
Akio Miyamoto
Keyword(s):  
Binding Free Energy ◽  
Spike Protein ◽  
The Novel ◽  
Angiotensin Converting Enzyme 2 ◽  
Risk Of Death ◽  
Main Protease ◽  
The World ◽  
Novel Coronavirus ◽  
Very High ◽  
Potential Use

Abstract The novel coronavirus disease (COVID-19) presently poses significant concerns around the world. Latest reports show that the degree of disease and mortality of COVID-19 infected patients may vary from gender to gender with a very high risk of death for seniors. It was hypothesized that sex steroid hormones estradiol (E2), progesterone (P4), testosterone (T), and dexamethasone (DEX) may change the interaction of coronavirus spike protein (CSP) with angiotensin converting enzyme-2 (ACE2). Data showed that E2 was more strongly to interact with the main protease of the coronavirus, while T had the lowest affinity for CSP. The binding energy of the CSP to ACE2 was increased in the presence of steroids; the greatest increase was observed by DEX and E2. The binding free energy of the CSP to ACE2 was the highest in the presence of E2 and DEX. Together, the interaction between CSP and ACE2 can be disrupted by E2 and to a greater extent by DEX, in part explaining the lower incidence of COVID-19 infection in women than men. The potential use of E2 and DEX to reduce coronavirus attachment to ACE2 in the early phase of the coronavirus invasion needs to be clinically investigated.

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.

scholarly journals Identification of potential inhibitors of coronavirus SARS-CoV-2 using the methods of virtual screening and molecular modeling

2020 ◽  
Vol 64 (3) ◽  
pp. 308-316
Author(s):  
A. M. Andrianov ◽  
Yu. V. Kornoushenko ◽  
A. D. Karpenko ◽  
A. V. Tuzikov
Keyword(s):  
Molecular Modeling ◽  
Virtual Screening ◽  
Etiologic Agent ◽  
The Novel ◽  
Chemical Structures ◽  
Main Protease ◽  
Structural And Functional Properties ◽  
Novel Coronavirus ◽  
Potential Inhibitors ◽  
Effective Drugs

To find small-molecule compounds that can simulate the structural and functional properties of the high affinity X77 ligand of the main protease of SARS-CoV-2 - etiologic agent of COVID-19, the virtual screening of 9 molecular libraries of the Pharmit web server containing over 213.5 million chemical structures was performed. Using molecular modeling, the neutralizing activity of the identified molecules was evaluated, resulting in 5 leader compounds promising for synthesis and testing for antiviral activity. The data obtained indicate that these compounds may be used as basic structures for the development of effective drugs to treat the novel coronavirus infection.

scholarly journals Assessing potential inhibitors of SARS-CoV-2 main protease from available drugs using free energy perturbation simulations

RSC Advances ◽  
2020 ◽  
Vol 10 (66) ◽  
pp. 40284-40290
Author(s):  
Son Tung Ngo ◽  
Hung Minh Nguyen ◽  
Le Thi Thuy Huong ◽  
Pham Minh Quan ◽  
Vi Khanh Truong ◽  
...  
Keyword(s):  
Free Energy ◽  
Binding Affinity ◽  
Free Energy Perturbation ◽  
The Novel ◽  
Main Protease ◽  
Energy Perturbation ◽  
Novel Coronavirus ◽  
Potential Inhibitors

Free Energy Pertubation (FEP) can be used to accurately predict the binding affinity of a ligand to the main protease (Mpro) of the novel coronavirus SARS-CoV-2.

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.

scholarly journals Novel Small-Molecule Scaffolds as Candidates against the SARS Coronavirus 2 Main Protease: A Fragment-Guided in Silico Approach

Molecules ◽  
2020 ◽  
Vol 25 (23) ◽  
pp. 5501
Author(s):  
Teresa L. Augustin ◽  
Roxanna Hajbabaie ◽  
Matthew T. Harper ◽  
Taufiq Rahman
Keyword(s):  
In Silico ◽  
3D Structure ◽  
The Novel ◽  
Health Crisis ◽  
Protein Ligand Interactions ◽  
Main Protease ◽  
Ligand Interactions ◽  
Spanish Flu ◽  
Active Fragments ◽  
Novel Coronavirus

The ongoing pandemic caused by the novel coronavirus has been the greatest global health crisis since the Spanish flu pandemic of 1918. Thus far, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in over 1 million deaths, and there is no cure or vaccine to date. The recently solved crystal structure of the SARS-CoV-2 main protease has been a major focus for drug-discovery efforts. Here, we present a fragment-guided approach using ZINCPharmer, where 17 active fragments known to bind to the catalytic centre of the SARS-CoV-2 main protease (SARS-CoV-2 Mpro) were used as pharmacophore queries to search the ZINC databases of natural compounds and natural derivatives. This search yielded 134 hits that were then subjected to multiple rounds of in silico analyses, including blind and focused docking against the 3D structure of the main protease. We scrutinised the poses, scores, and protein–ligand interactions of 15 hits and selected 7. The scaffolds of the seven hits were structurally distinct from known inhibitor scaffolds, thus indicating scaffold novelty. Our work presents several novel scaffolds as potential candidates for experimental validation against SARS-CoV-2 Mpro.

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.

Comparative docking of SARS-CoV-2 receptors antagonists from repurposing drugs

2020 ◽  
Author(s):  
Micael Davi Lima de Oliveira ◽  
Kelson Mota Teixeira de Oliveira
Keyword(s):  
World Health Organisation ◽  
World Health ◽  
Lung Cells ◽  
The Novel ◽  
High Modulation ◽  
Main Protease ◽  
The World ◽  
Novel Coronavirus ◽  
Viral Receptors ◽  
Theoretical Results

According to the World Health Organisation, until 16 June, 2020, the number of confirmed and notified cases of COVID-19 has already exceeded 7.9 million with approximately 434 thousand deaths worldwide. This research aimed to find repurposing antagonists, that may inhibit the activity of the main protease (Mpro) of the SARS-CoV-2 virus, as well as partially modulate the ACE2 receptors largely found in lung cells, and reduce viral replication by inhibiting Nsp12 RNA polymerase. Docking molecular simulations were performed among a total of 60 structures, most of all, published in the literature against the novel coronavirus. The theoretical results indicated that, in comparative terms, paritaprevir, ivermectin, ledipasvir, and simeprevir, are among the most theoretical promising drugs in remission of symptoms from the disease. Furthermore, also corroborate indinavir to the high modulation in viral receptors. The second group of promising drugs includes remdesivir and azithromycin. The repurposing drugs HCQ and chloroquine were not effective in comparative terms to other drugs, as monotherapies, against SARS-CoV-2 infection.

Coronavirus: Towards controlling of the pandemic - Indian scenario

2020 ◽  
Vol 11 (SPL1) ◽  
pp. 462-468
Author(s):  
Latika kothari ◽  
Sanskruti Wadatkar ◽  
Roshni Taori ◽  
Pavan Bajaj ◽  
Diksha Agrawal
Keyword(s):  
Control Measures ◽  
The Novel ◽  
Medical Treatments ◽  
Health Crisis ◽  
The Public ◽  
Infection Control Measures ◽  
The Social ◽  
Asking Questions ◽  
The Government ◽  
Novel Coronavirus

Coronavirus disease 2019 (COVID-19) is a communicable infection caused by the novel coronavirus resulting in severe acute respiratory syndrome coronavirus 2 (SARS-CoV). It was recognized to be a health crisis for the general population of international concern on 30th January 2020 and conceded as a pandemic on 11th March 2020. India is taking various measures to fight this invisible enemy by adopting different strategies and policies. To stop the COVID-19 from spreading, the Home Affairs Ministry and the health ministry, of India, has issued the nCoV 19 guidelines on travel. Screening for COVID-19 by asking questions about any symptoms, recent travel history, and exposure. India has been trying to get testing kits available. The government of India has enforced various laws like the social distancing, Janata curfew, strict lockdowns, screening door to door to control the spread of novel coronavirus. In this pandemic, innovative medical treatments are being explored, and a proper vaccine is being hunted to deal with the situation. Infection control measures are necessary to prevent the virus from further spreading and to help control the current situation. Thus, this review illustrates and explains the criteria provided by the government of India to the awareness of the public to prevent the spread of COVID-19.

Role of key point Mutations in Receptor Binding Domain of SARS-CoV-2 Spike Glycoprotein

2020 ◽  
Vol 20 ◽  
Author(s):  
Bipin Singh
Keyword(s):  
Receptor Binding ◽  
Point Mutations ◽  
Binding Domain ◽  
Receptor Binding Domain ◽  
Spike Glycoprotein ◽  
Angiotensin Converting Enzyme 2 ◽  
Recent Outbreak ◽  
Novel Coronavirus ◽  
Genomic Similarity

: The recent outbreak of novel coronavirus (SARS-CoV-2 or 2019-nCoV) and its worldwide spread is posing one of the major threats to human health and the world economy. It has been suggested that SARS-CoV-2 is similar to SARSCoV based on the comparison of the genome sequence. Despite the genomic similarity between SARS-CoV-2 and SARSCoV, the spike glycoprotein and receptor binding domain in SARS-CoV-2 shows the considerable difference compared to SARS-CoV, due to the presence of several point mutations. The analysis of receptor binding domain (RBD) from recently published 3D structures of spike glycoprotein of SARS-CoV-2 (Yan, R., et al. (2020); Wrapp, D., et al. (2020); Walls, A. C., et al. (2020)) highlights the contribution of a few key point mutations in RBD of spike glycoprotein and molecular basis of its efficient binding with human angiotensin-converting enzyme 2 (ACE2).

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