scholarly journals Rapid Identification of Potential Inhibitors of SARS-CoV-2 Main Protease by Deep Docking of 1.3 Billion Compounds

2020 ◽  
Author(s):  
Anh-Tien Ton ◽  
Francesco Gentile ◽  
Michael Hsing ◽  
Fuqiang Ban ◽  
Artem Cherkasov
Keyword(s):  
Rapid Identification ◽  
Molecular Structures ◽  
Drug Candidates ◽  
Learning Platform ◽  
Main Protease ◽  
The World ◽  
Novel Coronavirus ◽  
Potential Inhibitors ◽  
Small Molecule Therapeutics ◽  
Novel Drug

<div>The recently emerged 2019 Novel Coronavirus (SARS-CoV-2) and associated COVID-19 disease cause serious or even fatal respiratory tract infection and yet no FDA-approved therapeutics or effective treatment is currently available to effectively combat the outbreak. This urgent situation is pressing the world to respond with the development of novel vaccine or a small molecule therapeutics for SARS-CoV-2. Along these efforts, the structure of SARS-CoV-2 main protease (Mpro) has been rapidly resolved and made publicly available to facilitate global efforts to develop novel drug candidates.</div><div>In recent month, our group has developed a novel deep learning platform – Deep Docking (DD) which enables very fast docking of billions of molecular structures and provides up to 6,000X enrichment on the top-predicted ligands compared to conventional docking workflow (without notable loss of information on potential hits). In the current work we applied DD to entire 1.3 billion compounds from ZINC15 library to identify top 1,000 potential ligands for SARS-CoV-2 Mpro. The compounds are made publicly available for further characterization and development by scientific community.</div>

scholarly journals Rapid Identification of Potential Inhibitors of SARS-CoV-2 Main Protease by Deep Docking of 1.3 Billion Compounds

2020 ◽  
Author(s):  
Anh-Tien Ton ◽  
Francesco Gentile ◽  
Michael Hsing ◽  
Fuqiang Ban ◽  
Artem Cherkasov
Keyword(s):  
Rapid Identification ◽  
Molecular Structures ◽  
Drug Candidates ◽  
Learning Platform ◽  
Main Protease ◽  
The World ◽  
Novel Coronavirus ◽  
Potential Inhibitors ◽  
Small Molecule Therapeutics ◽  
Novel Drug

<div>The recently emerged 2019 Novel Coronavirus (SARS-CoV-2) and associated COVID-19 disease cause serious or even fatal respiratory tract infection and yet no FDA-approved therapeutics or effective treatment is currently available to effectively combat the outbreak. This urgent situation is pressing the world to respond with the development of novel vaccine or a small molecule therapeutics for SARS-CoV-2. Along these efforts, the structure of SARS-CoV-2 main protease (Mpro) has been rapidly resolved and made publicly available to facilitate global efforts to develop novel drug candidates.</div><div>In recent month, our group has developed a novel deep learning platform – Deep Docking (DD) which enables very fast docking of billions of molecular structures and provides up to 6,000X enrichment on the top-predicted ligands compared to conventional docking workflow (without notable loss of information on potential hits). In the current work we applied DD to entire 1.3 billion compounds from ZINC15 library to identify top 1,000 potential ligands for SARS-CoV-2 Mpro. The compounds are made publicly available for further characterization and development by scientific community.</div>

scholarly journals Drug repurposing and polypharmacology to fight SARS-CoV-2 through the inhibition of the main protease

2020 ◽  
Author(s):  
Luca Pinzi ◽  
Annachiara Tinivella ◽  
Fabiana Caporuscio ◽  
Giulio Rastelli
Keyword(s):  
Crystal Structure ◽  
Therapeutic Indication ◽  
Severe Disease ◽  
Drug Repurposing ◽  
Drug Candidates ◽  
Main Protease ◽  
The World ◽  
Novel Coronavirus ◽  
Potential Inhibitors ◽  
Drugbank Database

Abstract There is an urgent need to develop therapeutic options to fight the outbreak of a novel Coronavirus (SARS-CoV-2), which causes a disease named COVID-19 and is spreading rapidly around the world. Drug repurposing can significantly accelerate the identification of drug candidates suitable for clinical evaluation. Moreover, drugs with polypharmacological effects may increase antiviral activity and/or counteract severe disease complications concurrently affecting COVID-19 patients. Herein, we present the results of a computational drug repurposing campaign in search for potential inhibitors of the main protease of SARS-CoV-2. To this aim, the complete DrugBank database, including drug metabolites, was docked to the recently solved crystal structure of the SARS-CoV-2 Mpro and the results were post-processed by using our in-house tool BEAR. Here we report 32 promising drugs that could be repositioned to fight SARS-CoV-2. Some of them have already entered clinical trials against COVID-19, thus supporting our results, but the vast majority of the selected compounds is new and has never been considered before. For each repurposed compound its therapeutic relevance and the potential beneficial polypharmacological effects that may arise thanks to its original therapeutic indication are thoroughly discussed.

scholarly journals Drug repurposing and polypharmacology to fight SARS-CoV-2 through the inhibition of the main protease

2020 ◽  
Author(s):  
Luca Pinzi ◽  
Annachiara Tinivella ◽  
Fabiana Caporuscio ◽  
Giulio Rastelli
Keyword(s):  
Clinical Trials ◽  
Antiviral Activity ◽  
Therapeutic Indication ◽  
Drug Repurposing ◽  
Drug Candidates ◽  
Main Protease ◽  
The World ◽  
Novel Coronavirus ◽  
Potential Inhibitors ◽  
Selection Of

Abstract Therapeutic options are urgently needed to fight the outbreak of a novel coronavirus (SARS-CoV-2), which causes the COVID-19 disease and is spreading rapidly around the world. Drug repurposing can significantly accelerate the identification of drug candidates suitable for clinical evaluation. Moreover, polypharmacological effects may increase antiviral activity and/or counteract severe complications concurrently affecting COVID-19 patients. Herein, we present the results of a computational drug repurposing campaign in search of potential inhibitors of the main protease of SARS-CoV-2. The screening allowed the selection of 22 promising drugs. Some of them have already entered clinical trials, but the vast majority of the identified compounds are new and have never been considered before. For each repurposed compound, its therapeutic relevance and potential beneficial polypharmacological effects that may arise due to its original therapeutic indication are thoroughly discussed.

scholarly journals Drug Repurposing and Polypharmacology to Fight SARS-CoV-2 Through Inhibition of the Main Protease

2021 ◽  
Vol 12 ◽  
Author(s):  
Luca Pinzi ◽  
Annachiara Tinivella ◽  
Fabiana Caporuscio ◽  
Giulio Rastelli
Keyword(s):  
Clinical Trials ◽  
Antiviral Activity ◽  
Inhibitory Activity ◽  
Therapeutic Indication ◽  
Drug Repurposing ◽  
Drug Candidates ◽  
Main Protease ◽  
The World ◽  
Potential Inhibitors ◽  
Late Stages

The outbreak of a new coronavirus (SARS-CoV-2), which is responsible for the COVID-19 disease and is spreading rapidly around the world, urgently requires effective therapeutic treatments. In this context, drug repurposing represents a valuable strategy, as it enables accelerating the identification of drug candidates with already known safety profiles, possibly aiding in the late stages of clinical evaluation. Moreover, therapeutic treatments based on drugs with beneficial multi-target activities (polypharmacology) may show an increased antiviral activity or help to counteract severe complications concurrently affecting COVID-19 patients. In this study, we present the results of a computational drug repurposing campaign that aimed at identifying potential inhibitors of the main protease (Mpro) of the SARS-CoV-2. The performedin silicoscreening allowed the identification of 22 candidates with putative SARS-CoV-2 Mproinhibitory activity. Interestingly, some of the identified compounds have recently entered clinical trials for COVID-19 treatment, albeit not being assayed for their SARS-CoV-2 antiviral activity. Some candidates present a polypharmacology profile that may be beneficial for COVID-19 treatment and, to the best of our knowledge, have never been considered in clinical trials. For each repurposed compound, its therapeutic relevance and potential beneficial polypharmacological effects that may arise due to its original therapeutic indication are thoroughly discussed.

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 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 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.

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.

In Silico Approaches for Novel Drug Discovery Against Coronavirus by Employing the Hybrid Molecular Technique: A Review

2021 ◽  
pp. 1-8
Author(s):  
Noor ul Amin Mohsin ◽  
Muhammad Irfan ◽  
Muhammad Naeem Aamir
Keyword(s):  
In Silico ◽  
Antiviral Agent ◽  
Molecular Technique ◽  
The Novel ◽  
Hybrid Molecules ◽  
The World ◽  
Being There ◽  
Novel Coronavirus ◽  
Novel Drug ◽  
Day By Day

The coronavirus disease (COVID-19) is causing havoc all around the world. The number of active cases and deaths is increasing day by day. The novel coronavirus (CoV) is the causative agent of this disease. For the time being, there is no specific antiviral agent for the cure of COVID-19. A variety of drugs are being repurposed to counteract this disease. Scientists all over the world are striving to get some ideal molecules against this pandemic. Some hybrid molecules have been designed by coupling the privileged scaffolds of known antiviral and antimalarial drugs. This review deals with the hybrid molecules that have been designed and evaluated against the known targets of CoV by in silico techniques.

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