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  1. Article ; Online: Potential RNA-dependent RNA polymerase inhibitors as prospective therapeutics against SARS-CoV-2.

    Pokhrel, Rudramani / Chapagain, Prem / Siltberg-Liberles, Jessica

    Journal of medical microbiology

    2020  Volume 69, Issue 6, Page(s) 864–873

    Abstract: Introduction. ...

    Abstract Introduction.
    MeSH term(s) Animals ; Antiviral Agents/pharmacology ; Antiviral Agents/therapeutic use ; Betacoronavirus/drug effects ; Betacoronavirus/enzymology ; Betacoronavirus/genetics ; Betacoronavirus/physiology ; COVID-19 ; Coronavirus Infections/drug therapy ; Coronavirus Infections/virology ; Drug Evaluation, Preclinical/methods ; Drug Synergism ; Humans ; Molecular Conformation ; Pandemics ; Phylogeny ; Pneumonia, Viral/drug therapy ; Pneumonia, Viral/virology ; RNA-Dependent RNA Polymerase/antagonists & inhibitors ; RNA-Dependent RNA Polymerase/drug effects ; Rifampin/pharmacology ; SARS-CoV-2 ; Sequence Alignment ; Sequence Analysis, Protein ; Virginiamycin/analogs & derivatives ; Virginiamycin/pharmacology ; Virus Replication/drug effects
    Chemical Substances Antiviral Agents ; Virginiamycin (11006-76-1) ; quinupristin (23OW28RS7P) ; RNA-Dependent RNA Polymerase (EC 2.7.7.48) ; Rifampin (VJT6J7R4TR)
    Keywords covid19
    Language English
    Publishing date 2020-05-29
    Publishing country England
    Document type Journal Article
    ZDB-ID 218356-0
    ISSN 1473-5644 ; 0022-2615
    ISSN (online) 1473-5644
    ISSN 0022-2615
    DOI 10.1099/jmm.0.001203
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

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  2. Article: Potential RNA-dependent RNA polymerase inhibitors as prospective therapeutics against SARS-CoV-2

    Pokhrel, Rudramani / Chapagain, Prem / Siltberg-Liberles, Jessica

    J Med Microbiol

    Abstract: ... anti-SARS-CoV-2 therapeutic. At present, we have no evidence that this drug is effective against SARS ... with the US Food and Drug Administration (FDA)-approved drugs targeting the RNA-dependent RNA polymerase (RdRP), a critical enzyme ... Introduction. The emergence of SARS-CoV-2 has taken humanity off guard. Following an outbreak ...

    Abstract Introduction. The emergence of SARS-CoV-2 has taken humanity off guard. Following an outbreak of SARS-CoV in 2002, and MERS-CoV about 10 years later, SARS-CoV-2 is the third coronavirus in less than 20 years to cross the species barrier and start spreading by human-to-human transmission. It is the most infectious of the three, currently causing the COVID-19 pandemic. No treatment has been approved for COVID-19. We previously proposed targets that can serve as binding sites for antiviral drugs for multiple coronaviruses, and here we set out to find current drugs that can be repurposed as COVID-19 therapeutics.Aim. To identify drugs against COVID-19, we performed an in silico virtual screen with the US Food and Drug Administration (FDA)-approved drugs targeting the RNA-dependent RNA polymerase (RdRP), a critical enzyme for coronavirus replication.Methodology. Initially, no RdRP structure of SARS-CoV-2 was available. We performed basic sequence and structural analysis to determine if RdRP from SARS-CoV was a suitable replacement. We performed molecular dynamics simulations to generate multiple starting conformations that were used for the in silico virtual screen. During this work, a structure of RdRP from SARS-CoV-2 became available and was also included in the in silico virtual screen.Results. The virtual screen identified several drugs predicted to bind in the conserved RNA tunnel of RdRP, where many of the proposed targets were located. Among these candidates, quinupristin is particularly interesting because it is expected to bind across the RNA tunnel, blocking access from both sides and suggesting that it has the potential to arrest viral replication by preventing viral RNA synthesis. Quinupristin is an antibiotic that has been in clinical use for two decades and is known to cause relatively minor side effects.Conclusion. Quinupristin represents a potential anti-SARS-CoV-2 therapeutic. At present, we have no evidence that this drug is effective against SARS-CoV-2 but expect that the biomedical community will expeditiously follow up on our in silico findings.
    Keywords covid19
    Publisher WHO
    Document type Article
    Note WHO #Covidence: #436403
    Database COVID19

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  3. Book ; Online: Potential RNA-dependent RNA polymerase inhibitors as prospective therapeutics against SARS-CoV-2

    Pokhrel, Rudramani / Chapagain, Prem / Siltberg-Liberles, Jessica

    Coronavirus Research at FIU

    2020  

    Abstract: ... anti-SARS-CoV-2 therapeutic. At present, we have no evidence that this drug is effective against SARS ... with the US Food and Drug Administration (FDA)-approved drugs targeting the RNA-dependent RNA polymerase (RdRP), a critical enzyme ... Introduction. The emergence of SARS-CoV-2 has taken humanity off guard. Following an outbreak ...

    Abstract Introduction. The emergence of SARS-CoV-2 has taken humanity off guard. Following an outbreak of SARS-CoV in 2002, and MERS-CoV about 10 years later, SARS-CoV-2 is the third coronavirus in less than 20 years to cross the species barrier and start spreading by human-to-human transmission. It is the most infectious of the three, currently causing the COVID-19 pandemic. No treatment has been approved for COVID-19. We previously proposed targets that can serve as binding sites for antiviral drugs for multiple coronaviruses, and here we set out to find current drugs that can be repurposed as COVID-19 therapeutics. Aim. To identify drugs against COVID-19, we performed an in silico virtual screen with the US Food and Drug Administration (FDA)-approved drugs targeting the RNA-dependent RNA polymerase (RdRP), a critical enzyme for coronavirus replication. Methodology. Initially, no RdRP structure of SARS-CoV-2 was available. We performed basic sequence and structural analysis to determine if RdRP from SARS-CoV was a suitable replacement. We performed molecular dynamics simulations to generate multiple starting conformations that were used for the in silico virtual screen. During this work, a structure of RdRP from SARS-CoV-2 became available and was also included in the in silico virtual screen. Results. The virtual screen identified several drugs predicted to bind in the conserved RNA tunnel of RdRP, where many of the proposed targets were located. Among these candidates, quinupristin is particularly interesting because it is expected to bind across the RNA tunnel, blocking access from both sides and suggesting that it has the potential to arrest viral replication by preventing viral RNA synthesis. Quinupristin is an antibiotic that has been in clinical use for two decades and is known to cause relatively minor side effects. Conclusion. Quinupristin represents a potential anti-SARS-CoV-2 therapeutic. At present, we have no evidence that this drug is effective against SARS-CoV-2 but expect that the biomedical community will expeditiously follow up on our in silico findings.
    Keywords Medicine and Health Sciences ; covid19
    Subject code 572
    Publishing date 2020-05-29T07:00:00Z
    Publisher FIU Digital Commons
    Publishing country us
    Document type Book ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article: In silico evaluation of potential intervention against SARS-CoV-2 RNA-dependent RNA polymerase.

    Kapoor, Shreya / Singh, Anurag / Gupta, Vandana

    Physics and chemistry of the earth (2002)

    2022  Volume 129, Page(s) 103350

    Abstract: ... against the SARS-CoV-2 RdRp. Our results also re-validate already reported molecules like 2 ... and contain the spread of this deadly virus. Nsp12 or RNA-dependent RNA polymerase (RdRp) is ... poorly to existing vaccines and ever swelling newer waves of infection, SARS-CoV-2 is posing difficult ...

    Abstract Background: With few available effective interventions, emergence of novel mutants responding poorly to existing vaccines and ever swelling newer waves of infection, SARS-CoV-2 is posing difficult challenges to mankind. This mandates development of newer and effective therapeutics to prevent loss of life and contain the spread of this deadly virus. Nsp12 or RNA-dependent RNA polymerase (RdRp) is a suitable druggable target as it plays a central role in viral replication.
    Methodology: Catalytically important conserved amino acid residues of RdRp were delineated through a comprehensive literature search and multiple sequence alignments. PDB ID 7BV2 was used to create binding pockets using SeeSAR and to generate docked poses of the FDA approved drugs on the receptor and estimating their binding affinity and other properties.
    Result: In silico
    Conclusion: This study aimed to widen the prospect of interventions against the SARS-CoV-2 RdRp. Our results also re-validate already reported molecules like 2-Deoxy-D-glucose as a similar molecule 2-deoxy-2-fluoro-D-glucose is picked up in this study. Additionally, ribavirin and lamivudine, already known antivirals with polymerase inhibition activity are also picked up as the top leads. Selected potent inhibitors of RdRp hold promise to cater for any future coronavirus-outbreak subject to
    Language English
    Publishing date 2022-12-15
    Publishing country England
    Document type Journal Article
    ZDB-ID 208855-1
    ISSN 1474-7065 ; 0079-1946
    ISSN 1474-7065 ; 0079-1946
    DOI 10.1016/j.pce.2022.103350
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  5. Article: Discovering Potential RNA Dependent RNA Polymerase Inhibitors as Prospective Drugs Against COVID-19: An in silico Approach.

    Saha, Satabdi / Nandi, Rajat / Vishwakarma, Poonam / Prakash, Amresh / Kumar, Diwakar

    Frontiers in pharmacology

    2021  Volume 12, Page(s) 634047

    Abstract: ... for emergency use, are currently in development against SARS-CoV-2, their safety and efficacy data is still ... COVID-19, caused by Severe Acute Respiratory Syndrome Corona Virus 2, is declared a Global Pandemic ... in a very preliminary stage to recognize them as a new treatment, which demands an utmost emergency ...

    Abstract COVID-19, caused by Severe Acute Respiratory Syndrome Corona Virus 2, is declared a Global Pandemic by WHO in early 2020. In the present situation, though more than 180 vaccine candidates with some already approved for emergency use, are currently in development against SARS-CoV-2, their safety and efficacy data is still in a very preliminary stage to recognize them as a new treatment, which demands an utmost emergency for the development of an alternative anti-COVID-19 drug
    Language English
    Publishing date 2021-02-26
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2587355-6
    ISSN 1663-9812
    ISSN 1663-9812
    DOI 10.3389/fphar.2021.634047
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  6. Article ; Online: Suramin, penciclovir, and anidulafungin exhibit potential in the treatment of COVID-19 via binding to nsp12 of SARS-CoV-2.

    Dey, Sanjay Kumar / Saini, Manisha / Dhembla, Chetna / Bhatt, Shruti / Rajesh, A Sai / Anand, Varnita / Das, Hirendra Kumar / Kundu, Suman

    Journal of biomolecular structure & dynamics

    2021  Volume 40, Issue 24, Page(s) 14067–14083

    Abstract: ... the RNA-dependent RNA polymerase activity of SARS-CoV-2, a key therapeutic target for coronaviruses ... recent experimental evidences indicate that these drugs exhibit antiviral efficacy against SARS-CoV-2 ... enzyme outlined in this investigation, indicates that they might have a prospective therapeutic potential ...

    Abstract COVID-19, for which no confirmed therapeutic agents are available, has claimed over 48,14,000 lives globally. A feasible and quicker method to resolve this problem may be 'drug repositioning'. We investigated selected FDA and WHO-EML approved drugs based on their previously promising potential as antivirals, antibacterials or antifungals. These drugs were docked onto the nsp12 protein, which reigns the RNA-dependent RNA polymerase activity of SARS-CoV-2, a key therapeutic target for coronaviruses. Docked complexes were reevaluated using MM-GBSA analysis and the top three inhibitor-protein complexes were subjected to 100 ns long molecular dynamics simulation followed by another round of MM-GBSA analysis. The RMSF plots, binding energies and the mode of physicochemical interaction of the active site of the protein with the drugs were evaluated. Suramin, Penciclovir, and Anidulafungin were found to bind to nsp12 with similar binding energies as that of Remdesivir, which has been used as a therapy for COVID-19. In addition, recent experimental evidences indicate that these drugs exhibit antiviral efficacy against SARS-CoV-2. Such evidence, along with the significant and varied physical interactions of these drugs with the key viral enzyme outlined in this investigation, indicates that they might have a prospective therapeutic potential in the treatment of COVID-19 as monotherapy or combination therapy with Remdesivir.
    MeSH term(s) Humans ; SARS-CoV-2 ; COVID-19 ; Anidulafungin ; Suramin ; Molecular Docking Simulation ; Antiviral Agents/chemistry
    Chemical Substances Anidulafungin (9HLM53094I) ; penciclovir (359HUE8FJC) ; Suramin (6032D45BEM) ; Antiviral Agents
    Language English
    Publishing date 2021-11-16
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 49157-3
    ISSN 1538-0254 ; 0739-1102
    ISSN (online) 1538-0254
    ISSN 0739-1102
    DOI 10.1080/07391102.2021.2000498
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2093: Show issues Location:
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  7. Book ; Online: Suramin, Penciclovir and Anidulafungin bind nsp12, which governs the RNA-dependent-RNA polymerase activity of SARS-CoV-2, with similar interaction energy as Remdesivir-triphosphate, indicating potential in the treatment of COVID-19 infection

    Dey, Sanjay Kumar / Saini, Manisha / Dhembla, Chetna / Bhatt, Shruti / Rajesh, A. Sai / Anand, Varnita / Das, Hirendra Kumar / Kundu, Suman

    2020  

    Abstract: ... that these drugs exhibit antiviral efficacy against SARS-CoV-2. Thus, they might have a prospective therapeutic ... polymerase activity of SARS-CoV-2 and is one of the major therapeutic targets for corona viruses. Inhibitor ... were docked onto the three-dimensional structure of nsp12 protein, which reigns the RNA-dependent RNA ...

    Abstract Structured abstract:Introduction: COVID-19, for which no vaccine or confirmed therapeutic agents are available, has claimed over 7,30,000 lives globally. A feasible and quicker method to resolve this problem may be ‘drug repositioning’.Areas covered: We investigated selected FDA and WHO-EML approved drugs based on their previously promising potential as antivirals, antibacterials or antifungals. These drugs were docked onto the three-dimensional structure of nsp12 protein, which reigns the RNA-dependent RNA polymerase activity of SARS-CoV-2 and is one of the major therapeutic targets for corona viruses. Inhibitor-protein complexes were also subjected to molecular dynamics simulation. The binding energies and the mode of interaction of the active site of the protein with the drugs were evaluated.Results: Suramin, Penciclovir and Anidulafungin were found to bind to nsp12 with similar binding energies as that of Remdesivir, which is currently being used in the treatment of COVID-19. In addition, recent experimental evidences indicate that these drugs exhibit antiviral efficacy against SARS-CoV-2. Thus, they might have a prospective therapeutic potential against the key viral enzyme.Expert opinion: Repurposed drugs will provide viable options for the treatment of COVID-19 and insight into the molecular mechanisms by which these potential drug candidates exhibit anti-SARSCoV-2 activity.
    Keywords covid19
    Publisher Center for Open Science
    Publishing country us
    Document type Book ; Online
    DOI 10.31219/osf.io/urxwh
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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