This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Research Article
Search for therapeutics against COVID 19 targeting SARS-CoV-2 papain-like protease: an in silico study
Manabendra Dutta Choudhury
Assam University
Corresponding Author
ORCiD: https://orcid.org/0000-0002-9472-0572
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: The global pandemic of novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an enveloped, positive-sense, single-stranded RNA betacoronavirus of the family Coronaviridae. Papain-like protease (PLpro) of SARS CoV-2 is an important target of COVID-19 because it is a multifunctional cysteine protease essential for coronaviral replication.
Large numbers of phytochemicals with varied chemical structures isolated from medicinal plants have been shown to possess antiviral activity. Some of these phytochemicals have been chosen on the basis of literature survey for this study. Reported inhibitors of the papain-like protease are taken as control and for QSAR study.
Methods: Three dimensional structure of target was downloaded from Protein Data Bank and docked with phytochemicals & inhibitors by using software FlexX. Inhibitors of the papain-like protease were taken from binding database and QSAR analysis was performed by using EasyQSAR software.
Results: Six phytochemicals: Baicalin, Rutin, Biopterin, Licoleafol, Luteolin and Quercetin shows stable bonding pattern with the target in compare to known inhibitors as it shows least score in docking, forms maximum number of hydrogen bonds with the active residues of the receptor. The predicted IC50 values of the phytochemicals are also better than the known inhibitors.
Conclusion: Based on present observation of docking score of both phytochemicals and known inhibitors, IC50 value of known inhibitors and predicted IC50 of phytochemicals, we suggests above mentioned six phytochemicals may be the Papain-like protease (PLpro) targeted potent drug leads against Covid-19.
Keywords
COVID-19, SARS-CoV-2, Papain-like protease, phytochemicals, molecular docking, QSAR
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
Figure 9
Figure 10
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 05 Jun, 2020
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Learn more about our company.
This is a preprint. It has not completed peer review.
Research Article
Search for therapeutics against COVID 19 targeting SARS-CoV-2 papain-like protease: an in silico study
Manabendra Dutta Choudhury
Assam University
Corresponding Author
ORCiD: https://orcid.org/0000-0002-9472-0572
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 05 Jun, 2020
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: The global pandemic of novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an enveloped, positive-sense, single-stranded RNA betacoronavirus of the family Coronaviridae. Papain-like protease (PLpro) of SARS CoV-2 is an important target of COVID-19 because it is a multifunctional cysteine protease essential for coronaviral replication.
Large numbers of phytochemicals with varied chemical structures isolated from medicinal plants have been shown to possess antiviral activity. Some of these phytochemicals have been chosen on the basis of literature survey for this study. Reported inhibitors of the papain-like protease are taken as control and for QSAR study.
Methods: Three dimensional structure of target was downloaded from Protein Data Bank and docked with phytochemicals & inhibitors by using software FlexX. Inhibitors of the papain-like protease were taken from binding database and QSAR analysis was performed by using EasyQSAR software.
Results: Six phytochemicals: Baicalin, Rutin, Biopterin, Licoleafol, Luteolin and Quercetin shows stable bonding pattern with the target in compare to known inhibitors as it shows least score in docking, forms maximum number of hydrogen bonds with the active residues of the receptor. The predicted IC50 values of the phytochemicals are also better than the known inhibitors.
Conclusion: Based on present observation of docking score of both phytochemicals and known inhibitors, IC50 value of known inhibitors and predicted IC50 of phytochemicals, we suggests above mentioned six phytochemicals may be the Papain-like protease (PLpro) targeted potent drug leads against Covid-19.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
Figure 9
Figure 10