scholarly journals Computational screening for potential drug candidates against the SARS-CoV-2 main protease

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 514
Author(s):  
Bruno Silva Andrade ◽  
Preetam Ghosh ◽  
Debmalya Barh ◽  
Sandeep Tiwari ◽  
Raner José Santana Silva ◽  
...  
Keyword(s):  
Natural Compounds ◽  
Potential Drug ◽  
Drug Candidates ◽  
Positive Effects ◽  
Computational Screening ◽  
Main Protease ◽  
Zinc Database ◽  
Structural Assembly

Background: SARS-CoV-2 is the causal agent of the current coronavirus disease 2019 (COVID-19) pandemic. They are enveloped, positive-sense, single-stranded RNA viruses of the Coronaviridae family. Proteases of SARS-CoV-2 are necessary for viral replication, structural assembly, and pathogenicity. The approximately 33.8 kDa Mpro protease of SARS-CoV-2 is a non-human homologue and is highly conserved among several coronaviruses, indicating that Mpro could be a potential drug target for Coronaviruses. Methods: Herein, we performed computational ligand screening of four pharmacophores (OEW, remdesivir, hydroxychloroquine and N3) that are presumed to have positive effects against SARS-CoV-2 Mpro protease (6LU7), and also screened 50,000 natural compounds from the ZINC Database dataset against this protease target. Results: We found 40 pharmacophore-like structures of natural compounds from diverse chemical classes that exhibited better affinity of docking as compared to the known ligands. The 11 best selected ligands, namely ZINC1845382, ZINC1875405, ZINC2092396, ZINC2104424, ZINC44018332, ZINC2101723, ZINC2094526, ZINC2094304, ZINC2104482, ZINC3984030, and ZINC1531664, are mainly classified as beta-carboline, alkaloids, and polyflavonoids, and all displayed interactions with dyad CYS145 and HIS41 from the protease pocket in a similar way as other known ligands. Conclusions: Our results suggest that these 11 molecules could be effective against SARS-CoV-2 protease and may be subsequently tested in vitro and in vivo to develop novel drugs against this virus.

scholarly journals Computational screening for potential drug candidates against the SARS-CoV-2 main protease

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 514 ◽  
Author(s):  
Bruno Silva Andrade ◽  
Preetam Ghosh ◽  
Debmalya Barh ◽  
Sandeep Tiwari ◽  
Raner José Santana Silva ◽  
...  
Keyword(s):  
Natural Compounds ◽  
Potential Drug ◽  
Drug Candidates ◽  
Positive Effects ◽  
Computational Screening ◽  
Main Protease ◽  
Zinc Database ◽  
Structural Assembly

Background: SARS-CoV-2 is the causal agent of the current coronavirus disease 2019 (COVID-19) pandemic. They are enveloped, positive-sense, single-stranded RNA viruses of the Coronaviridae family. Proteases of SARS-CoV-2 are necessary for viral replication, structural assembly, and pathogenicity. The approximately 33.8 kDa Mpro protease of SARS-CoV-2 is a non-human homologue and is highly conserved among several coronaviruses, indicating that Mpro could be a potential drug target for Coronaviruses. Methods: Herein, we performed computational ligand screening of four pharmacophores (OEW, remdesivir, hydroxychloroquine and N3) that are presumed to have positive effects against SARS-CoV-2 Mpro protease (6LU7), and also screened 50,000 natural compounds from the ZINC Database dataset against this protease target. Results: We found 40 pharmacophore-like structures of natural compounds from diverse chemical classes that exhibited better affinity of docking as compared to the known ligands. The 11 best selected ligands, namely ZINC1845382, ZINC1875405, ZINC2092396, ZINC2104424, ZINC44018332, ZINC2101723, ZINC2094526, ZINC2094304, ZINC2104482, ZINC3984030, and ZINC1531664, are mainly classified as beta-carboline, alkaloids, and polyflavonoids, and all displayed interactions with dyad CYS145 and HIS41 from the protease pocket in a similar way as other known ligands. Conclusions: Our results suggest that these 11 molecules could be effective against SARS-CoV-2 protease and may be subsequently tested in vitro and in vivo to develop novel drugs against this virus.

scholarly journals Computational Screening for Potential Drug Candidates Against SARS-CoV-2 Main Protease

2020 ◽  
Author(s):  
Bruno Andrade ◽  
Preetam Ghosh ◽  
Debmalya Barth ◽  
Sandeep Tiwari ◽  
Raner José Santana Silva ◽  
...  
Keyword(s):  
Potential Drug ◽  
Drug Candidates ◽  
Positive Effects ◽  
Computational Screening ◽  
Main Protease ◽  
Zinc Database ◽  
Novel Drugs ◽  
Structural Assembly

Background: SARS-CoV-2 that are the causal agent of a current pandemic are enveloped, positive-sense, single-stranded RNA viruses of the Coronaviridae family. Proteases of SARS-CoV-2 are necessary for viral replication, structural assembly and pathogenicity. The ~33.8KDa Mpro protease of SARS-CoV-2 is a non-human homologue and highly conserved among several coronaviruses indicating Mpro could be a potential drug target for Coronaviruses.Methods: Here we performed computational ligand screening of four pharmacophores (OEW, Remdesivir, Hydroxycholoquine and N3) that are presumed to have positive effects against SARS-CoV-2 Mpro protease (6LU7) and also screened 50,000 molecules from the ZINC Database dataset against this protease target.Results: We found 40 pharmacophore-like structures of natural compounds from diverse chemical classes that exhibited better affinity of docking as compared to the known ligands. The 10 best selected ligands namely, ZINC1845382, ZINC1875405, ZINC2092396, ZINC2104424, ZINC44018332, ZINC2101723, ZINC2094526, ZINC2094304, ZINC2104482, ZINC3984030, and ZINC1531664, are mainly classified as β-carboline, Alkaloids and Polyflavonoids, and all of them displayed interactions with dyad CYS145 and HIS41 from the protease pocket in a similar way as with other known ligands.Conclusion: Our results suggest that these 10 molecules could be effective against SARS-CoV-2 protease and may be tested in vitro and in vivo to develop novel drugs against this virus.

scholarly journals Computational Screening for Potential Drug Candidates Against SARS-CoV-2 Main Protease

2020 ◽  
Author(s):  
Bruno Andrade ◽  
Preetam Ghosh ◽  
Debmalya Barth ◽  
Sandeep Tiwari ◽  
Raner José Santana Silva ◽  
...  
Keyword(s):  
Potential Drug ◽  
Drug Candidates ◽  
Positive Effects ◽  
Computational Screening ◽  
Main Protease ◽  
Zinc Database ◽  
Novel Drugs ◽  
Structural Assembly

Background: SARS-CoV-2 that are the causal agent of a current pandemic are enveloped, positive-sense, single-stranded RNA viruses of the Coronaviridae family. Proteases of SARS-CoV-2 are necessary for viral replication, structural assembly and pathogenicity. The ~33.8KDa Mpro protease of SARS-CoV-2 is a non-human homologue and highly conserved among several coronaviruses indicating Mpro could be a potential drug target for Coronaviruses.Methods: Here we performed computational ligand screening of four pharmacophores (OEW, Remdesivir, Hydroxycholoquine and N3) that are presumed to have positive effects against SARS-CoV-2 Mpro protease (6LU7) and also screened 50,000 molecules from the ZINC Database dataset against this protease target.Results: We found 40 pharmacophore-like structures of natural compounds from diverse chemical classes that exhibited better affinity of docking as compared to the known ligands. The 10 best selected ligands namely, ZINC1845382, ZINC1875405, ZINC2092396, ZINC2104424, ZINC44018332, ZINC2101723, ZINC2094526, ZINC2094304, ZINC2104482, ZINC3984030, and ZINC1531664, are mainly classified as β-carboline, Alkaloids and Polyflavonoids, and all of them displayed interactions with dyad CYS145 and HIS41 from the protease pocket in a similar way as with other known ligands.Conclusion: Our results suggest that these 10 molecules could be effective against SARS-CoV-2 protease and may be tested in vitro and in vivo to develop novel drugs against this virus.

scholarly journals Natural Compounds from Djiboutian Medicinal Plants as Inhibitors of COVID-19 by in Silico Investigations

2020 ◽  
Author(s):  
abdirahman elmi ◽  
S. al jawad sayem ◽  
Mohamed Ahmed ◽  
fatouma mohamed
Keyword(s):  
Medicinal Plants ◽  
Natural Compounds ◽  
Binding Energies ◽  
Receptor Binding Domain ◽  
Global Pandemic ◽  
Main Protease ◽  
Target Sites ◽  
Better Than

The new coronavirus type SARS-Cov 2 (severe acute respiratory syndrome), which appeared in autumn 2019 in China, became a global pandemic in a few months. In this work, we looked for the potential anti SARS-Cov 2 of the compounds isolated from three Djiboutian medicinal plants namely Acacia seyal, Cymbopogon commutatus, and Indigofera caerulea. For this we carried out a docking with nine biomolecules, β-Sitosterol , Quercetin, Catechin, Lupeol, Rutin, Kaempferol, Gallic acid, Piperitone and Limonene on three target sites which are SARS-CoV-2 main protease (Mp), SARS-CoV-2 receptor binding domain (RBD) and human furin protease. These targets are chosen because of their role in the process of penetration of the virus into human cells and its multiplication. The phenolic compounds have a very good afinity on these three target sites with binding energies of up to -9.098 kcal/mol for rutin on SARS-CoV-2 Mp, much better than the two reference drugs hydroxychloroquine (-5.816 kcal / mol) and remdesivir (-7.194 kcal/mol). These natural compounds do not present toxicities and can be used pending In vitro and In vivo evaluations.

scholarly journals NATURAL COMPOUNDS FROM DJIBOUTIAN MEDICINAL PLANTS AS INHIBITORS OF COVID-19 BY IN SILICO INVESTIGATIONS

2020 ◽  
pp. 52-57
Author(s):  
ABDIRAHMAN ELMI ◽  
S. AL-JAWAD SAYEM ◽  
MOHAMED AHMED ◽  
FATOUMA ABDOUL-LATIF
Keyword(s):  
Medicinal Plants ◽  
Natural Compounds ◽  
Binding Energies ◽  
Pharmacokinetic Parameters ◽  
Global Pandemic ◽  
Main Protease ◽  
Target Sites ◽  
Better Than

Objective: The new coronavirus type SARS-Cov 2 (severe acute respiratory syndrome), which appeared in autumn 2019 in China, became a global pandemic in a few months. In this work, we looked for the potential anti SARS-Cov 2 of the compounds isolated from three Djiboutian medicinal plants, namely Acacia seyal, Cymbopogon commutatus, and Indigofera caerulea. Methods: We carried out a molecular docking with nine biomolecules, β-Sitosterol, Quercetin, Catechin, Lupeol, Rutin, Kaempferol, Gallic acid, Piperitone and Limonene on three target sites which are SARS-CoV-2 main protease (Mp), SARS-CoV-2 receptor-binding domain (RBD) and human furin protease. These targets are chosen because of their role in the process of penetration of the virus into human cells and its multiplication. Moreover, the predictions of pharmacokinetic parameters as well as toxicological properties have been determined using an online bioinformatics tool named SwissADME and AdmetSAR respectively. Results: The phenolic compounds have a very good affinity on these three target sites with binding energies of up to-9.098 kcal/mol for rutin on SARS-CoV-2 Mp, much better than the two reference drugs hydroxychloroquine (-5.816 kcal/mol) and remdesivir (-7.194 kcal/mol). Except for β-Sitosterol, the tested biomolecules have weak toxicity. Conclusion: These natural compounds can be used against covid 19 pending In vitro and In vivo evaluations.

scholarly journals Structure-Based Virtual Screening and Molecular Dynamics of Phytochemicals Derived from Saudi Medicinal Plants to Identify Potential COVID-19 Therapeutics

2020 ◽  
Author(s):  
MUBARAK ALAMRI ◽  
Ali Altharawi ◽  
Alhumaidi B. Alabbas ◽  
Manal A. Alossaimi ◽  
Safar M. Alqahtani
Keyword(s):  
Virtual Screening ◽  
Medicinal Plants ◽  
In Vivo Studies ◽  
Effective Vaccine ◽  
Traditional Medicines ◽  
Drug Candidates ◽  
Computational Screening ◽  
Novel Coronavirus

Coronavirus disease 2019 (COVID-19) has affected almost every country in the world by causing a global pandemic with a high mortality rate. Lack of an effective vaccine and/or antiviral drugs against SARS-CoV-2, the causative agent, has severely hampered the response to this novel coronavirus. Natural products have long been used in traditional medicines to treat various diseases, and purified phytochemicals from medicinal plants provide a valuable scaffold for the discovery of new drug leads. In the present study, we performed a computational screening of an in-house database composed of ~1000 phytochemicals derived from traditional Saudi medicinal plants with recognised antiviral activity. Structure-based virtual screening was carried out against three druggable SARS-CoV-2 targets, viral RNAdependent RNA polymerase (RdRp), 3-chymotrypsin-like cysteine protease (3CLpro) and papain like protease (PLpro) to identify putative inhibitors that could facilitate the development of potential anti-COVID-19 drug candidates. Computational analyses identified three compounds inhibiting each target, with binding affinity scores ranging from-9.9 to -6.5 kcal/mol. Among these, luteolin 7-rutinoside, chrysophanol 8-(6-galloylglucoside) and kaempferol 7-(6’’-galloylglucoside) bound efficiently to RdRp, while chrysophanol 8-(6galloylglucoside), 3,4,5-tri-O-galloylquinic acid and mulberrofuran G interacted strongly with 3CLpro, and withanolide A, isocodonocarpine and calonysterone bound tightly to PLpro. These potential drug candidates will be subjected to further in vitro and in vivo studies and may assist the development of effective anti-COVID-19 drugs.

scholarly journals THE INVENTION OF CANDIDATE COMPOUNDS FROM STRYCHNINE BUSH, PINEAPPLE AND GINGER AS THE MAIN PROTEASE RECEPTOR INHIBITOR OF COVID-19 VIRUS

2020 ◽  
Vol 8 (Spl-1-SARS-CoV-2) ◽  
pp. S202-S209
Author(s):  
Novi Yantih ◽  
◽  
Linda Erlina ◽  
Esti Mulatsari ◽  
Wahono Sumaryono ◽  
...  
Keyword(s):  
Active Metabolite ◽  
Zingiber Officinale ◽  
Binding Pocket ◽  
Ananas Comosus ◽  
Potential Candidate ◽  
Drug Candidates ◽  
Main Protease ◽  
Receptor Inhibitor

The emerging coronavirus, Covid-19, has become a worldwide pandemic. The existence of the Covid-19 virus pandemic in the world demands the need to identify and characterize new drug candidates to address the health problem caused by the Covid-19 virus. This study aims to find candidate compounds from strychnine bush (Strychnos lucida), pineapple (Ananas comosus), and ginger (Zingiber officinale) acting as the Mpro receptor inhibitor on Covid-19 virus based on docking modeling. The docking process is carried out using a protein with the pdb code 6LU7, a crystal main protein protease (Mpro) of the Covid-19 which binds to the N3 molecule as an inhibitor based on computational tests. The docking process is conducted using N3 comparison, favipiravir, active metabolite remdesivir, and hydroxychloroquine. The docking result shows that the compounds, ananas 26, zingiberenol, and zingiberol have lower docking energy compared to native ligand (N3), favipiravir, active metabolite remdesivir, and hydroxychloroquine. Ananas 26 compound has the most hydrogen bonds with the Mpro active amino acid residue of the Covid-19 virus, namely: HIS163, ASN142, ASP187, TYR54, and HIS41. This makes Ananas 26 more stable in binding pocket enzymes and more effective in inhibiting enzyme performance than other compounds and positive controls. Potential candidate compounds as SARS-CoV-2 Main Protease inhibitors, ananas 26 from pineapple and zingiberenol as well as zingiberol from ginger, can then undergo potential inhibitor tests by in vitro and in vivo methods on SARS-CoV-2.

scholarly journals Natural Compounds from Djiboutian Medicinal Plants as Inhibitors of COVID-19 by in Silico Investigations

2020 ◽  
Author(s):  
abdirahman elmi ◽  
S. al jawad sayem ◽  
Mohamed Ahmed ◽  
fatouma mohamed
Keyword(s):  
Medicinal Plants ◽  
Natural Compounds ◽  
Binding Energies ◽  
Receptor Binding Domain ◽  
Global Pandemic ◽  
Main Protease ◽  
Target Sites ◽  
Better Than

The new coronavirus type SARS-Cov 2 (severe acute respiratory syndrome), which appeared in autumn 2019 in China, became a global pandemic in a few months. In this work, we looked for the potential anti SARS-Cov 2 of the compounds isolated from three Djiboutian medicinal plants namely Acacia seyal, Cymbopogon commutatus, and Indigofera caerulea. For this we carried out a docking with nine biomolecules, β-Sitosterol , Quercetin, Catechin, Lupeol, Rutin, Kaempferol, Gallic acid, Piperitone and Limonene on three target sites which are SARS-CoV-2 main protease (Mp), SARS-CoV-2 receptor binding domain (RBD) and human furin protease. These targets are chosen because of their role in the process of penetration of the virus into human cells and its multiplication. The phenolic compounds have a very good afinity on these three target sites with binding energies of up to -9.098 kcal/mol for rutin on SARS-CoV-2 Mp, much better than the two reference drugs hydroxychloroquine (-5.816 kcal / mol) and remdesivir (-7.194 kcal/mol). These natural compounds do not present toxicities and can be used pending In vitro and In vivo evaluations.

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