Comprehensive In Silico Screening of the Antiviral Potentialities of a New Humulene Glucoside from Asteriscus hierochunticus against SARS-CoV-2

Chromatographic fractionation of the methanolic extract of Asteriscus hierochunticus whole plant led to the identification of a new humulene glucoside (1). The chemical structure of the isolated compound was elucidated by IR, 1D, 2D NMR, and HRESIMS data analysis to be (-)-(2Z,6E,9E)8α-hydroxy-2,6,9-humulatrien-1(12)-olide. In this study, we report the in silico binding affinities of 1 against four different SARS-CoV-2 proteins (COVID-19 main protease (PDB ID: 6lu7), nonstructural protein (PDB ID: 6W4H), RNA-dependent RNA polymerase (PDB ID: 7BV2), and SARS-CoV-2 helicase (PDB ID: 5RMM)). The isolated compound showed excellent binding affinity values (ΔG) of −21.65, −20.05, −28.93, and −21.73 kcal/mol, respectively, against the target proteins compared to the cocrystallized ligands that exhibited ΔG values of −23.75, −17.65, −23.57, and −15.30 kcal/mol, respectively. Further in silico investigations of the isolated compound (1) for its ADMET and toxicity profiles revealed excellent drug likeliness. On the other hand, the results obtained from in vitro antitrypanosomal, antileishmanial, and antimalarial activities of (1) were not promising.

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In silico SCREENING OF Ziziphus spina-christi (L.) Desf. AND Strychnos ligustrine COMPOUNDS AS A PROTEASE INHIBITOR OF SARS-COV-2

Journal of Experimental Biology and Agricultural Sciences ◽

10.18006/2021.9(spl-2-icopmes_2020).s208.s214 ◽

2021 ◽

Vol 9 (Spl-2-ICOPMES_2020) ◽

pp. S208-S214

Author(s):

Novi Yantih ◽

◽

Uthami Syabillawati ◽

Esti Mulatsari ◽

Wahono Sumaryono ◽

...

Keyword(s):

In Silico ◽

Data Bank ◽

Binding Pocket ◽

In Vivo Studies ◽

In Silico Screening ◽

Main Protease ◽

Docking Method ◽

Inhibitory Site

Diseases caused by the coronavirus have become an important concern in early 2020. The coronavirus is a new type of virus that is included in the SARS-CoV-2 group. One of the possible mechanisms of SARS-CoV-2 inhibition involves protease receptors inhibition. This research was aimed to in silico screening of Ziziphus spina-christi (L.) Desf., and Strychnos ligustrine active ingredients as the main protease inhibitors of SARS-CoV-2 by assessing the ligand-binding affinity in the binding pocket of SARS-CoV-2 main protease protein. The molecular docking method is generally used to predict the inhibitory site and bonds formation. In the current study, some generally used antiviral compounds from the PDB (Protein Data Bank) were also used to compare the affinity strength of the test compound against the protease receptor (code of 5R7Y). The inhibitory activity against the main protease receptor proven by the ChemPLP score is more negative than the receptor’s native ligand and the comparison compounds. Jubanine B, a compound of Z. spina-christi has the most robust inhibition activity on the SARS-CoV-2 protease receptor. Results of this study can be concluded that this can be used to develop as a candidate for traditional medicine against SARS-CoV-2 but still it required some more in vitro and in vivo studies.

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In silico Screening of Food Bioactive Compounds to Predict Potential Inhibitors of COVID-19 Main protease (Mpro) and RNA-dependent RNA polymerase (RdRp)

10.26434/chemrxiv.12051927.v2 ◽

2020 ◽

Cited By ~ 4

Author(s):

Brahmaiah Pendyala ◽

Ankit Patras

Keyword(s):

Rna Polymerase ◽

Bioactive Compounds ◽

In Silico ◽

World Health ◽

Rna Dependent Rna Polymerase ◽

In Silico Screening ◽

Main Protease ◽

Health Organization

As novel corona virus (COVID-19) infections has spread throughout the world, world health organization (WHO) has announced COVID-19 as a pandemic infection. Henceforth investigators are conducting extensive research to find possible therapeutic agents against COVID-19. Main protease (Mpro) that plays an essential role in processing the polyproteins that are translated from the 2019-nCOV RNA and RNA-dependent RNA polymerase (RdRp) that catalyzes the replication of RNA from RNA template becomes as a potential targets for in silico screening of effective therapeutic compounds to COVID-19. In this study we used COVID-19 Docking Server to predict potential food bioactive compounds to inhibit Mpro and RdRp. The results showed that Phycocyanobilin, Riboflavin, Cyanidin, Daidzein, Genistein are potent inhibitor bioactive compounds to Mpro and RdRp in comparison to antiviral drugs. Though, further in vitro and/or in vivo research is required to validate the docking results.

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In silico Screening of Food Bioactive Compounds to Predict Potential Inhibitors of COVID-19 Main protease (Mpro) and RNA-dependent RNA polymerase (RdRp)

10.26434/chemrxiv.12051927 ◽

2020 ◽

Cited By ~ 1

Author(s):

Brahmaiah Pendyala ◽

Ankit Patras

Keyword(s):

Rna Polymerase ◽

Bioactive Compounds ◽

In Silico ◽

World Health ◽

Rna Dependent Rna Polymerase ◽

In Silico Screening ◽

Main Protease ◽

Health Organization

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In silico Screening of Food Bioactive Compounds to Predict Potential Inhibitors of COVID-19 Main protease (Mpro) and RNA-dependent RNA polymerase (RdRp)

10.26434/chemrxiv.12051927.v1 ◽

2020 ◽

Cited By ~ 1

Author(s):

Brahmaiah Pendyala ◽

Ankit Patras

Keyword(s):

Rna Polymerase ◽

Bioactive Compounds ◽

In Silico ◽

World Health ◽

Rna Dependent Rna Polymerase ◽

In Silico Screening ◽

Main Protease ◽

Health Organization

As novel corona virus (COVID-19) infections has spread throughout the world, world health organization (WHO) has announced COVID-19 as a pandemic infection. Henceforth investigators are conducting extensive research to find possible therapeutic agents against COVID-19. Main protease (Mpro) that plays an essential role in processing the polyproteins that are translated from the COVID-19 RNA becomes and RNA-dependent RNA polymerase (RdRp) that catalyzes the replication of RNA from RNA template as a potential targets for in silico screening of effective therapeutic compounds to COVID-19. In this study we used COVID-19 Docking Server to predict potential food bioactive compounds to inhibit Mpro and RdRp. The results showed that Phycocyanobilin, Riboflavin, Cyanidin, Daidzein, Genistein are potent inhibitor bioactive compounds to Mpro and RdRp in comparison to antiviral drugs. Though, further in vitro and/or in vivo research is required to validate the docking results.

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Identification of low micromolar SARS-CoV-2 Mpro inhibitors from hits identified by in silico screens

10.1101/2020.12.03.409441 ◽

2020 ◽

Author(s):

Giacomo G. Rossetti ◽

Marianna Ossorio ◽

Samia Barriot ◽

Laurence Tropia ◽

Vasilis S. Dionellis ◽

...

Keyword(s):

Life Cycle ◽

Inhibitory Activity ◽

In Silico ◽

Chemical Structure ◽

Chemical Compounds ◽

Activity Assay ◽

Biochemical Assays ◽

Main Protease ◽

Thermal Shift

ABSTRACTMpro, also known as 3CLpro, is the main protease of the SARS-CoV-2 coronavirus and, as such, is essential for the viral life cycle. Two studies have each screened and ranked in silico more than one billion chemical compounds in an effort to identify putative inhibitors of Mpro. More than five hundred of the seven thousand top-ranking hits were synthesized by an external supplier and examined with respect to their activity in two biochemical assays: a protease activity assay and a thermal shift assay. Two clusters of chemical compounds with Mpro inhibitory activity were identified. An additional five hundred molecules, analogues of the compounds in the two clusters described above, were also synthesized and characterized in vitro. The study of the analogues revealed that the compounds of the first cluster acted by denaturing Mpro and might denature other proteins as well. In contrast, the compounds of the second cluster targeted Mpro with much greater specificity and enhanced its melting temperature, consistent with the formation of stable Mpro-inhibitor complexes. The most active compounds of the second cluster exhibited IC50 values between 4 and 7 μM and their chemical structure suggests that they could serve as leads for the development of potent Mpro inhibitors.

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Berberis lyceum and Fumaria indica: in vitro cytotoxicity, antioxidant activity, and in silico screening of their selected phytochemicals as novel hepatitis C virus nonstructural protein 5A inhibitors

Journal of Biomolecular Structure and Dynamics ◽

10.1080/07391102.2021.1902395 ◽

2021 ◽

pp. 1-25

Author(s):

Koloko Brice Landry ◽

Somayya Tariq ◽

Ayesha Malik ◽

Muhammad Sufyan ◽

Usman Ali Ashfaq ◽

...

Keyword(s):

Antioxidant Activity ◽

Hepatitis C Virus ◽

Hepatitis C ◽

In Silico ◽

Nonstructural Protein ◽

In Vitro Cytotoxicity ◽

In Silico Screening ◽

Nonstructural Protein 5A

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Novel Spiro/non-Spiro Pyranopyrazoles: Eco-Friendly Synthesis, In-vitro Anticancer Activity, DNA Binding, and In-silico Docking Studies

Current Bioactive Compounds ◽

10.2174/1573407213666170828165512 ◽

2019 ◽

Vol 15 (2) ◽

pp. 257-267 ◽

Cited By ~ 3

Author(s):

Paritosh Shukla ◽

Ashok Sharma ◽

Leena Fageria ◽

Rajdeep Chowdhury

Keyword(s):

Anticancer Activity ◽

Anticancer Agents ◽

In Silico ◽

Antimicrobial Agents ◽

Docking Studies ◽

Bioactive Molecules ◽

Microwave Assisted Synthesis ◽

Binding Affinities ◽

In Silico Docking

Background: Cancer being a deadly disease, many reports of new chemical entities are available. Pyranopyrazole (PPZ) compounds have also been disclosed as bioactive molecules but mainly as antimicrobial agents. Based on one previous report and our interest in anticancer drug design, we decided to explore PPZs as anticancer agents. To the best of our knowledge, we found that a comprehensive study, involving synthesis, in-vitro biological activity determination, exploration of the mechanism of inhibition and finally in-silico docking studies, was missing in earlier reports. This is what the present study intends to accomplish. Methods: Ten spiro and eleven non-spiro PPZ molecules were synthesized by environment-friendly multicomponent reaction (MCR) strategy. After subjecting each of the newly synthesized molecules to Hep3b hepatocellular carcinoma cell lines assay, we selectively measured the Optical Density (OD) of the most active ones. Then, the compound exhibiting the best activity was docked against human CHK- 1 protein to get an insight into the binding affinities and a quick structure activity relationship (SAR) of the PPZs. Results: The two series of spiro and non-spiro PPZs were easily synthesized in high yields using microwave assisted synthesis and other methods. Among the synthesized compounds, most compounds showed moderate to good anticancer activity against the MTT assay. After performing the absorbance studies we found that the non-spiro molecules showed better apoptosis results and appeared to bind to DNA causing disruption in their structures. Finally, the docking results of compound 5h (having N,Ndimethylamino substituted moiety) clearly showed good binding affinities as predicted by our experimental findings. Conclusion: The paper describes a comprehensive synthesis, in-vitro and docking studies done on new PPZs. The newly synthesized series of spiro and non-spiro PPZs were found to possess antineoplasmic activity as evinced by the studies on hep3b cells. Also, the UV visible absorbance study gave clues to the possible binding of these molecules to the DNA. Docking studies corroborated well with the experimental results. Thus, these new molecules appear to be potential anticancer agents, but further studies are required to substantiate and elaborate on these findings.

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Virtual Screening, Molecular docking and in-silico ADME-Tox analysis for identification of potential main protease (Mpro) enzyme inhibitors

Anti-Infective Agents ◽

10.2174/2211352518999201208201854 ◽

2020 ◽

Vol 18 ◽

Author(s):

Debadash Panigrahi ◽

Ganesh Prasad Mishra

Keyword(s):

Molecular Docking ◽

Virtual Screening ◽

In Silico ◽

Data Bank ◽

Future Research ◽

Reference Compound ◽

Unexpected Death ◽

Main Protease ◽

In Silico Admet

Objective:: Recent pandemic caused by SARS-CoV-2 described in Wuhan China in December-2019 spread widely almost all the countries of the world. Corona virus (COVID-19) is causing the unexpected death of many peoples and severe economic loss in several countries. Virtual screening based on molecular docking, drug-likeness prediction, and in silico ADMET study has become an effective tool for the identification of small molecules as novel antiviral drugs to treat diseases. Methods:: In the current study, virtual screening was performed through molecular docking for identifying potent inhibitors against Mpro enzyme from the ZINC library for the possible treatment of COVID-19 pandemic. Interestingly, some compounds are identified as possible anti-covid-19 agents for future research. 350 compounds were screened based on their similarity score with reference compound X77 from ZINC data bank and were subjected to docking with crystal structure available of Mpro enzyme. These compounds were then filtered by their in silico ADME-Tox and drug-likeness prediction values. Result:: Out of these 350 screened compounds, 10 compounds were selected based on their docking score and best docked pose in comparison to the reference compound X77. In silico ADME-Tox and drug likeliness predictions of the top compounds were performed and found to be excellent results. All the 10 screened compounds showed significant binding pose with the target enzyme main protease (Mpro) enzyme and satisfactory pharmacokinetic and toxicological properties. Conclusion:: Based on results we can suggest that the identified compounds may be considered for therapeutic development against the COVID-19 virus and can be further evaluated for in vitro activity, preclinical, clinical studies and formulated in a suitable dosage form to maximize their bioavailability.

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

Letters in Drug Design & Discovery ◽

10.2174/1570180818666210317162502 ◽

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.

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