Anti-SARS and anti-HCV drugs repurposing against the Papain-like protease of the newly emerged coronavirus (2019-nCoV)

Elfiky, Abdo A.; Ibrahim, Noha

doi:10.21203/rs.2.23280/v1

Cited by 26 publications

(25 citation statements)

References 17 publications

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“…As a vital enzyme in the process of coronavirus replication and infection of the host, PLpro is an accepted target for coronavirus inhibitors. It is very important for targeting PLpro to treat coronavirus infections (6,7). Stripping ubiquitin and ISG15 from host-cell proteins to assist coronaviruses in their evasion of the host innate immune responses is an added function of PLpro.…”

Section: Sars-cov-2 Is a New Member Of Betacorona Virus In The Coronamentioning

confidence: 99%

Search for therapeutics against COVID 19 targeting SARS-CoV-2 papain-like protease: an in silico study

Laskar¹,

Choudhury²

2020

Preprint

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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.

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Section: Sars-cov-2 Is a New Member Of Betacorona Virus In The Coronamentioning

confidence: 99%

Search for therapeutics against COVID 19 targeting SARS-CoV-2 papain-like protease: an in silico study

Laskar¹,

Choudhury²

2020

Preprint

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“…However, it was reported to inhibit autophagy and may potentiate tissue damage [ 86 ]. Another molecular docking of three inhibitors of SARS-CoV PLpro (GRL-0667, GRL-0617, and mycophenolic acid) and three inhibitors of HCV PLpro (telaprevir, boceprevir, and grazoprevir) revealed that each compound can bind to the active site of SARS-CoV-2 PLpro, which makes them prospective drugs [ 87 , 88 ]. Several compounds from Chinese medical herbs have also been found to bind with SARS-CoV-2 PLpro, 3CLpro, and S protein.…”

Section: Current Development Of Inhibitors Of Cov Plpromentioning

confidence: 99%

Papain-Like Proteases as Coronaviral Drug Targets: Current Inhibitors, Opportunities, and Limitations

Petushkova

Zamyatnin

2020

Pharmaceuticals

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Papain-like proteases (PLpro) of coronaviruses (CoVs) support viral reproduction and suppress the immune response of the host, which makes CoV PLpro perspective pharmaceutical targets. Their inhibition could both prevent viral replication and boost the immune system of the host, leading to the speedy recovery of the patient. Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the third CoV outbreak in the last 20 years. Frequent mutations of the viral genome likely lead to the emergence of more CoVs. Inhibitors for CoV PLpro can be broad-spectrum and can diminish present and prevent future CoV outbreaks as PLpro from different CoVs have conservative structures. Several inhibitors have been developed to withstand SARS-CoV and Middle East respiratory syndrome CoV (MERS-CoV). This review summarizes the structural features of CoV PLpro, the inhibitors that have been identified over the last 20 years, and the compounds that have the potential to become novel effective therapeutics against CoVs in the near future.

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“…Papain-like Protease (PLpro) is characterized in different coronaviruses, including SARS and MERS [35].…”

Section: Papain-like Protease Inhibitorsmentioning

confidence: 99%

Screening of Potential Inhibitors of Covid-19 with Repurposing Approach Via Molecular Docking

Alizadehmohajer

Sadeghi

Najafgholian

et al. 2020

Preprint

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Background: 2019-nCoV (COVID-19) is a pandemic disease with a high infectivity and mortality. The prevention and treatment of COVID-19 have become urgent matters for consideration. It often takes several years to develop new drugs, or vaccines, based on the usual clinical trial process. This dwell-time can be shortened by repurposing previously approved drugs.Methods: We have designed and evaluated a bacterial biosensor expressing a luciferase We aimed to assess several available small-molecule; Abl kinase inhibitors, Janus kinase inhibitor, Dipeptidyl peptidase 4 inhibitors, RNA-dependent RNA polymerase inhibitors, and Papin-like Protease inhibitors, using binding simulation with proteins that might prove to be effective in inhibiting COVID-19 infection. The efficiency of inhibitors was evaluated based on docking scores using auto dock vina software.Results: Strong ligand-protein interactions were predicted among some of these drugs, such as Imatinib, Remdesivir, and Telaprevir, and this may render these compounds promising candidates. Some candidate drugs might be efficient in disease control (directly and indirectly) or in viral proteins attenuation. It is worth to highlight the powerful immunomodulatory role of Abivertinib that inhibits pro-inflammatory cytokine production that are associated with cytokine release syndrome (CRS) or cytokine storm and progression of COVID-19 infection.Conclusions: COVID-19 is similar to SARS-CoV, the potential role of Abl kinase inhibitors such as Imatinib in reducing SARS-CoV and MERS-CoV viral titers, immune regulatory function and the development of acute respiratory distress syndrome (ARDS) may indicate that these drugs may be useful for COVID-19. Moreover, Remdesivir, and Telaprevir have the most efficiency with their docked proteins in-silico as well although clinical trials are needed to confirm the effect of these drugs.

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Anti-SARS and anti-HCV drugs repurposing against the Papain-like protease of the newly emerged coronavirus (2019-nCoV)

Cited by 26 publications

References 17 publications

Search for therapeutics against COVID 19 targeting SARS-CoV-2 papain-like protease: an in silico study

Search for therapeutics against COVID 19 targeting SARS-CoV-2 papain-like protease: an in silico study

Papain-Like Proteases as Coronaviral Drug Targets: Current Inhibitors, Opportunities, and Limitations

Screening of Potential Inhibitors of Covid-19 with Repurposing Approach Via Molecular Docking

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