In silico evaluation of potential inhibitory activity of remdesivir, favipiravir, ribavirin and galidesivir active forms on SARS-CoV-2 RNA polymerase

Çeli̇k, İsmail; Erol, Meryem; Düzgün, Zekeriya

doi:10.1007/s11030-021-10215-5

Cited by 32 publications

(29 citation statements)

References 54 publications

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“…39 Celik et al (2021) investigated antiviral prodrugs such as favipiravir, remdesivir, galidesivir and ribavirin, and their triphosphate metabolites, for the viral RdRp inhibition. 40 According to molecular docking results, triphosphate active metabolite forms showed higher interaction than prodrug and other intermediate metabolites. 40 41 In conclusion, these authors found that favipiravir can bind to active sites of coronavirus RdRp proteins and replicated RNA terminals.…”

Section: Introductionmentioning

confidence: 99%

“…40 According to molecular docking results, triphosphate active metabolite forms showed higher interaction than prodrug and other intermediate metabolites. 40 41 In conclusion, these authors found that favipiravir can bind to active sites of coronavirus RdRp proteins and replicated RNA terminals. 41 In the same line, other in silico studies dedicated efforts in the study of drugs for COVID-19 treatment, such as favipiravir, remdesivir, among others.…”

Section: Introductionmentioning

confidence: 99%

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Theoretical insights into the effect of halogenated substituent on the electronic structure and spectroscopic properties of the favipiravir tautomeric forms and its implications for the treatment of COVID-19

et al. 2021

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Theoretical insights into the effect of halogenated substituent on the electronic structure and spectroscopic properties of the favipiravir tautomeric forms and its implications for the treatment of COVID-19

et al. 2021

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“…According to the authors, these metabolites have pharmacologic activity and are thought to be approximately as toxic as the non-metabolized drug 59 . Hu et al investigated the pharmacokinetic behavior and tissue distribution of Rendesivir and its metabolites 60 , as well as it is approached in other studies 61 , 62 .…”

Section: Resultsmentioning

confidence: 99%

Effect of drug metabolism in the treatment of SARS-CoV-2 from an entirely computational perspective

Jesus

Assis

Castro

et al. 2021

Sci Rep

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Understanding the effects of metabolism on the rational design of novel and more effective drugs is still a considerable challenge. To the best of our knowledge, there are no entirely computational strategies that make it possible to predict these effects. From this perspective, the development of such methodologies could contribute to significantly reduce the side effects of medicines, leading to the emergence of more effective and safer drugs. Thereby, in this study, our strategy is based on simulating the electron ionization mass spectrometry (EI-MS) fragmentation of the drug molecules and combined with molecular docking and ADMET models in two different situations. In the first model, the drug is docked without considering the possible metabolic effects. In the second model, each of the intermediates from the EI-MS results is docked, and metabolism occurs before the drug accesses the biological target. As a proof of concept, in this work, we investigate the main antiviral drugs used in clinical research to treat COVID-19. As a result, our strategy made it possible to assess the biological activity and toxicity of all potential by-products. We believed that our findings provide new chemical insights that can benefit the rational development of novel drugs in the future.

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“…RdRp is selected as a target to design crRNA for the application of CRISPR/Cas13-based therapeutics based on several reasons: 1) RdRp is a versatile enzyme for viral RNA replication and transcription of viral genome in host cells, which makes RdRp essential for viral survival and spread [3] , [24] ; 2) RdRp is considered to be a highly conserved enzyme across all RNA viruses and some DNA viruses, such as coronavirus, influenza virus, zika virus, hepatitis C virus [37] ; 3) RdRp has a very low mutation rate among COVID-19 patients ( Figure 1 ); 4) RdRp has no homologs in human cells and its RNA sequence shows an extremely low similarity with human transcriptome [38] ; 5) The essential role of RdRp for viral RNA replication and transcription makes it become a promising therapeutic target and many drugs are repurposed and developed to target it for COVID-19 treatment, such as remdesivir [22] , favipiravir [39] , ribavirin [40] , sofosbuvir [41] , and galidesivir [42] .…”

Section: Discussionmentioning

confidence: 99%

A one-step platform for screening high-efficient and minimal off-target CRISPR/Cas13 crRNAs to eradicate SARS-CoV-2 virus for treatment of COVID-19 patients

Gao

et al. 2022

Medical Hypotheses

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Coronavirus disease 2019 (COVID-19) is a new respiratory illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and now spreads globally. Currently, therapeutics and effective treatment options remain scarce and there is no proven drug to treat COVID-19. Targeting the positive-sense RNA genome and viral mRNAs of SARS-CoV-2 to simultaneously degrade viral genome templates for replication and viral mRNAs for essential gene expression would be a strategy to completely realize virus elimination. Type VI CRISPR enzymes Cas13 have recently been identified as programmable RNA-guided, RNA-targeting Cas proteins with nuclease activity that allows for RNA cleavage and degradation. The precise viral RNA detection and antiviral application of the CRISPR/Cas13 system depend on high-efficient and minimal off-target crRNAs. Although a computer-based algorithm has been applied for the design of crRNAs targeting SRAS-CoV-2, the experimental screening system to identify optimal crRNA is not available. We develop a one-step experimental screening system to identify high-efficient crRNAs with minimal off-target effects for CRISPR/Cas13-based SARS-CoV-2 elimination. This platform provides the foundation for CRISPR/Cas13-based diagnostics and therapeutics for COVID-19. This platform is versatile and could also be applied for crRNAs screening for other RNA viruses.

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In silico evaluation of potential inhibitory activity of remdesivir, favipiravir, ribavirin and galidesivir active forms on SARS-CoV-2 RNA polymerase

Cited by 32 publications

References 54 publications

Theoretical insights into the effect of halogenated substituent on the electronic structure and spectroscopic properties of the favipiravir tautomeric forms and its implications for the treatment of COVID-19

Theoretical insights into the effect of halogenated substituent on the electronic structure and spectroscopic properties of the favipiravir tautomeric forms and its implications for the treatment of COVID-19

Effect of drug metabolism in the treatment of SARS-CoV-2 from an entirely computational perspective

A one-step platform for screening high-efficient and minimal off-target CRISPR/Cas13 crRNAs to eradicate SARS-CoV-2 virus for treatment of COVID-19 patients

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