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  1. Article ; Online: Polymonoclonal (Not Polyclonal) Antibodies Derived from Convalescent Human B Cell Hybridomas Might Be a Better Therapeutic Option than Single Target Monoclonal Antibodies.

    Begum, Feroza / Ray, Upasana

    ACS pharmacology & translational science

    2020  Volume 3, Issue 4, Page(s) 786–787

    Abstract: Both human B cell hybridoma technology and convalescent plasma therapy are promising immunological tools for therapeutic interventions. Here we propose using antibody producing B cells from convalescent SARS-CoV2 patients for developing human B cell ... ...

    Abstract Both human B cell hybridoma technology and convalescent plasma therapy are promising immunological tools for therapeutic interventions. Here we propose using antibody producing B cells from convalescent SARS-CoV2 patients for developing human B cell hybridomas, and a combination of monoclonal antibodies against multiple immunogenic targets of SARS-CoV-2 spike protein might deliver an antibody cocktail for long-lasting therapeutic targeting.
    Keywords covid19
    Language English
    Publishing date 2020-07-24
    Publishing country United States
    Document type Journal Article
    ISSN 2575-9108
    ISSN (online) 2575-9108
    DOI 10.1021/acsptsci.0c00084
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: A substrate for a cell free in vitro assay system to screen drugs targeting trypsin like protease-based cleavage of SARS-CoV-2 spike glycoprotein and viral entry.

    Begum, Feroza / Srivastava, Amit K / Tripathi, Prem Prakash / Ray, Upasana

    Journal of medical virology

    2023  Volume 95, Issue 5, Page(s) e28796

    Abstract: Host proteases trypsin and trypsin-like proteases have been reported to facilitate the entry of coronavirus SARS-CoV-2 in its host cells. These protease enzymes cleave the viral surface glycoprotein, spike, leading to successful cell surface receptor ... ...

    Abstract Host proteases trypsin and trypsin-like proteases have been reported to facilitate the entry of coronavirus SARS-CoV-2 in its host cells. These protease enzymes cleave the viral surface glycoprotein, spike, leading to successful cell surface receptor attachment, fusion and entry of the virus in its host cell. The spike protein has protease cleavage sites between the two domains S1 and S2. Since the cleavage site is recognized by the host proteases, it can be a potential antiviral therapeutic target. Trypsin-like proteases play an important role in virus infectivity and the property of spike protein cleavage by trypsin and trypsin-like proteases can be used to design assays for screening of antiviral candidates against spike protein cleavage. Here, we have documented the development of a proof-of-concept assay system for screening drugs against trypsin/trypsin-like proteases that cleave spike protein between its S1 and S2 domains. The assay system developed uses a fusion substrate protein containing a NanoLuc luciferase reporter protein, the protease cleavage site between S1 and S2 domains of SARS-CoV-2 spike protein and a cellulose binding domain. The substrate protein can be immobilized on cellulose via the cellulose binding domain of the substrate. When trypsin and trypsin-like proteases cleave the substrate, the cellulose binding domain remain bound to the cellulose and the reporter protein is dislodged. Reporter assay using the released reporter protein is the read out of the protease activity. We have demonstrated the proof-of-concept using multiple proteases like trypsin, TMPRSS2, furin, cathepsin B, human airway trypsin and cathepsin L. A significant increment in fold change was observed with increasing enzyme concentration and incubation time. Introduction of increasing amounts of enzyme inhibitors in the reaction reduced the luminescent signal, thus validating the assay. Furthermore, we used SDS-PAGE and immunoblot analyses to study the cleavage band pattern and re-confirm the cleavage for enzymes tested in the assay. Taken together, we have tested an in-vitro assay system using the proposed substrate for screening drugs against trypsin like protease-based cleavage of SARS-CoV-2 spike glycoprotein. The assay system can also be potentially used for antiviral drug screening against any other enzyme that might cleave the used cleavage site.
    MeSH term(s) Humans ; Spike Glycoprotein, Coronavirus/metabolism ; Trypsin ; Virus Internalization ; SARS-CoV-2/metabolism ; COVID-19 ; Peptide Hydrolases
    Chemical Substances spike protein, SARS-CoV-2 ; Spike Glycoprotein, Coronavirus ; Trypsin (EC 3.4.21.4) ; Peptide Hydrolases (EC 3.4.-)
    Language English
    Publishing date 2023-05-23
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 752392-0
    ISSN 1096-9071 ; 0146-6615
    ISSN (online) 1096-9071
    ISSN 0146-6615
    DOI 10.1002/jmv.28796
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Book ; Online: Repurposing Nonnucleoside Antivirals Against SARS-CoV2 NSP12 (RNA Dependent RNA Polymerase) and Identification of Domain Specific Interactions

    Feroza Begum / UPASANA RAY

    2020  

    Abstract: The pandemic of SARS-CoV-2 has necessitated expedited research efforts towards finding potential antiviral targets and drug development measures. While new drug discovery is time consuming, drug repurposing has been a promising area for elaborate virtual ...

    Abstract The pandemic of SARS-CoV-2 has necessitated expedited research efforts towards finding potential antiviral targets and drug development measures. While new drug discovery is time consuming, drug repurposing has been a promising area for elaborate virtual screening and identification of existing FDA approved drugs that could possibly be used for targeting against functions of various proteins of SARS-CoV-2 virus. RNA dependent RNA polymerase (RdRp) is an important enzyme for the virus that mediates replication of the viral RNA. Inhibition of RdRp could inhibit viral RNA replication and thus new virus particle production. Here, we screened non-nucleoside antivirals and found three out of them to be strongest in binding to RdRp. We propose these three drugs as potential RdRp inhibitors based on the site of binding.
    Keywords Bioinformatics and Computational Biology ; SARS-CoV2 ; RdRp ; NSP12 ; drug repurposing ; covid19
    Publishing date 2020-07-27T13:10:42Z
    Document type Book ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Repurposing nonnucleoside antivirals against SARS-CoV2 NSP12 (RNA dependent RNA polymerase): In silico-molecular insight.

    Begum, Feroza / Srivastava, Amit Kumar / Ray, Upasana

    Biochemical and biophysical research communications

    2021  Volume 571, Page(s) 26–31

    Abstract: The pandemic of SARS-CoV-2 has necessitated expedited research efforts towards finding potential antiviral targets and drug development measures. While new drug discovery is time consuming, drug repurposing has been a promising area for elaborate virtual ...

    Abstract The pandemic of SARS-CoV-2 has necessitated expedited research efforts towards finding potential antiviral targets and drug development measures. While new drug discovery is time consuming, drug repurposing has been a promising area for elaborate virtual screening and identification of existing FDA approved drugs that could possibly be used for targeting against functions of various proteins of SARS-CoV-2 virus. RNA dependent RNA polymerase (RdRp) is an important enzyme for the virus that mediates replication of the viral RNA. Inhibition of RdRp could inhibit viral RNA replication and thus new virus particle production. Here, we screened non-nucleoside antivirals and found three out of them to be strongest in binding to RdRp out of which two retained binding even using molecular dynamic simulations. We propose these two drugs as potential RdRp inhibitors which need further in-depth testing.
    MeSH term(s) Amides/pharmacology ; Antiviral Agents/chemistry ; Antiviral Agents/pharmacology ; Benzimidazoles/pharmacology ; COVID-19/drug therapy ; COVID-19/virology ; Carbamates/pharmacology ; Catalytic Domain ; Computer Simulation ; Coronavirus RNA-Dependent RNA Polymerase/antagonists & inhibitors ; Coronavirus RNA-Dependent RNA Polymerase/chemistry ; Cyclopropanes/pharmacology ; Drug Evaluation, Preclinical ; Drug Repositioning ; Fluorenes/pharmacology ; Humans ; Lactams, Macrocyclic/pharmacology ; Molecular Docking Simulation ; Molecular Dynamics Simulation ; Pandemics ; Proline/analogs & derivatives ; Proline/pharmacology ; Protein Conformation ; Quinoxalines/pharmacology ; SARS-CoV-2/drug effects ; SARS-CoV-2/enzymology ; Sulfonamides/pharmacology
    Chemical Substances Amides ; Antiviral Agents ; Benzimidazoles ; Carbamates ; Cyclopropanes ; Fluorenes ; Lactams, Macrocyclic ; Quinoxalines ; Sulfonamides ; ledipasvir (013TE6E4WV) ; grazoprevir (4O2AB118LA) ; Proline (9DLQ4CIU6V) ; Coronavirus RNA-Dependent RNA Polymerase (EC 2.7.7.48) ; NSP12 protein, SARS-CoV-2 (EC 2.7.7.48) ; paritaprevir (OU2YM37K86)
    Language English
    Publishing date 2021-07-16
    Publishing country United States
    Document type Journal Article
    ZDB-ID 205723-2
    ISSN 1090-2104 ; 0006-291X ; 0006-291X
    ISSN (online) 1090-2104 ; 0006-291X
    ISSN 0006-291X
    DOI 10.1016/j.bbrc.2021.07.050
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Repurposing nonnucleoside antivirals against SARS-CoV2 NSP12 (RNA dependent RNA polymerase): In silico-molecular insight

    Begum, Feroza / Srivastava, Amit Kumar / Ray, Upasana

    Biochemical and biophysical research communications. 2021 Sept. 24, v. 571

    2021  

    Abstract: The pandemic of SARS-CoV-2 has necessitated expedited research efforts towards finding potential antiviral targets and drug development measures. While new drug discovery is time consuming, drug repurposing has been a promising area for elaborate virtual ...

    Abstract The pandemic of SARS-CoV-2 has necessitated expedited research efforts towards finding potential antiviral targets and drug development measures. While new drug discovery is time consuming, drug repurposing has been a promising area for elaborate virtual screening and identification of existing FDA approved drugs that could possibly be used for targeting against functions of various proteins of SARS-CoV-2 virus. RNA dependent RNA polymerase (RdRp) is an important enzyme for the virus that mediates replication of the viral RNA. Inhibition of RdRp could inhibit viral RNA replication and thus new virus particle production. Here, we screened non-nucleoside antivirals and found three out of them to be strongest in binding to RdRp out of which two retained binding even using molecular dynamic simulations. We propose these two drugs as potential RdRp inhibitors which need further in-depth testing.
    Keywords RNA ; RNA replication ; RNA-directed RNA polymerase ; Severe acute respiratory syndrome coronavirus 2 ; antiviral agents ; drug development ; pandemic ; research ; virion ; viruses
    Language English
    Dates of publication 2021-0924
    Size p. 26-31.
    Publishing place Elsevier Inc.
    Document type Article
    ZDB-ID 205723-2
    ISSN 0006-291X ; 0006-291X
    ISSN (online) 0006-291X
    ISSN 0006-291X
    DOI 10.1016/j.bbrc.2021.07.050
    Database NAL-Catalogue (AGRICOLA)

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  6. Article ; Online: Refining Network Lifetime of Wireless Sensor Network Using Energy-Efficient Clustering and DRL-Based Sleep Scheduling.

    Sinde, Ramadhani / Begum, Feroza / Njau, Karoli / Kaijage, Shubi

    Sensors (Basel, Switzerland)

    2020  Volume 20, Issue 5

    Abstract: Over the recent era, Wireless Sensor Network (WSN) has attracted much attention among industrialists and researchers owing to its contribution to numerous applications including military, environmental monitoring and so on. However, reducing the network ... ...

    Abstract Over the recent era, Wireless Sensor Network (WSN) has attracted much attention among industrialists and researchers owing to its contribution to numerous applications including military, environmental monitoring and so on. However, reducing the network delay and improving the network lifetime are always big issues in the domain of WSN. To resolve these downsides, we propose an Energy-Efficient Scheduling using the Deep Reinforcement Learning (DRL) (E
    Language English
    Publishing date 2020-03-10
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2052857-7
    ISSN 1424-8220 ; 1424-8220
    ISSN (online) 1424-8220
    ISSN 1424-8220
    DOI 10.3390/s20051540
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: Polymonoclonal (Not Polyclonal) Antibodies Derived from Convalescent Human B Cell Hybridomas Might Be a Better Therapeutic Option than Single Target Monoclonal Antibodies

    Begum, Feroza / Ray, Upasana

    ACS Pharmacol Transl Sci

    Abstract: Both human B cell hybridoma technology and convalescent plasma therapy are promising immunological tools for therapeutic interventions. Here we propose using antibody producing B cells from convalescent SARS-CoV2 patients for developing human B cell ... ...

    Abstract Both human B cell hybridoma technology and convalescent plasma therapy are promising immunological tools for therapeutic interventions. Here we propose using antibody producing B cells from convalescent SARS-CoV2 patients for developing human B cell hybridomas, and a combination of monoclonal antibodies against multiple immunogenic targets of SARS-CoV-2 spike protein might deliver an antibody cocktail for long-lasting therapeutic targeting.
    Keywords covid19
    Publisher WHO
    Document type Article
    Note WHO #Covidence: #711973
    Database COVID19

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  8. Article ; Online: Analyses of spike protein from first deposited sequences of SARS-CoV2 from West Bengal, India [version 2; peer review

    Arup Kumar Banerjee / Prem Prakash Tripathi / Upasana Ray / Feroza Begum / Dluya Thagriki / Debica Mukherjee / Sandeepan Das

    F1000Research, Vol

    2 approved, 1 approved with reservations]

    2023  Volume 9

    Abstract: India has recently started sequencing SARS-CoV2 genome from clinical isolates. Currently only few sequences are available from three states in India. Kerala was the first state to deposit complete sequence from two isolates followed by one from Gujarat. ... ...

    Abstract India has recently started sequencing SARS-CoV2 genome from clinical isolates. Currently only few sequences are available from three states in India. Kerala was the first state to deposit complete sequence from two isolates followed by one from Gujarat. On April 27, 2020, the first five sequences from the state of West Bengal (Eastern India) were deposited on GISAID, a global initiative for sharing avian flu data. In this study, we have analysed the spike protein sequences from all five isolates and also compared their similarities or differences with other sequences reported in India and with isolates of Wuhan origin. We report one unique mutation at position 723 and another at 1124 in the S2 domain of spike protein of the isolates from West Bengal only. There was one mutation downstream of the receptor binding domain at position 614 in S1 domain which was common with the sequence from Gujarat (a state of western India). Mutation in the S2 domain showed changes in the secondary structure of the spike protein at region of the mutation. We also studied molecular dynamics using normal mode analyses and found that this mutation decreases the flexibility of S2 domain. Since both S1 and S2 are important in receptor binding followed by entry in the host cells, such mutations may define the affinity or avidity of receptor binding.
    Keywords Spike ; India ; West Bengal ; Mutations ; eng ; Medicine ; R ; Science ; Q
    Subject code 612
    Language English
    Publishing date 2023-09-01T00:00:00Z
    Publisher F1000 Research Ltd
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Book ; Online: Repurposing Nonnucleoside Antivirals Against SARS-CoV2 NSP12 (RNA Dependent RNA Polymerase) and Identification of Domain Specific Interactions

    Begum, Feroza / RAY, UPASANA

    2020  

    Abstract: ... The pandemic of SARS-CoV-2 has necessitated expedited research efforts towards finding potential antiviral targets and drug development measures. While new drug discovery is time consuming, drug repurposing has been a promising area for elaborate ... ...

    Abstract

    The pandemic of SARS-CoV-2 has necessitated expedited research efforts towards finding potential antiviral targets and drug development measures. While new drug discovery is time consuming, drug repurposing has been a promising area for elaborate virtual screening and identification of existing FDA approved drugs that could possibly be used for targeting against functions of various proteins of SARS-CoV-2 virus. RNA dependent RNA polymerase (RdRp) is an important enzyme for the virus that mediates replication of the viral RNA. Inhibition of RdRp could inhibit viral RNA replication and thus new virus particle production. Here, we screened non-nucleoside antivirals and found three out of them to be strongest in binding to RdRp. We propose these three drugs as potential RdRp inhibitors based on the site of binding.


    Keywords covid19
    Publisher American Chemical Society (ACS)
    Publishing country us
    Document type Book ; Online
    DOI 10.26434/chemrxiv.12721634.v1
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Book ; Online: Repurposing Nonnucleoside Antivirals Against SARS-CoV2 NSP12 (RNA Dependent RNA Polymerase) and Identification of Domain Specific Interactions

    Begum, Feroza / RAY, UPASANA

    2020  

    Abstract: ... The pandemic of SARS-CoV-2 has necessitated expedited research efforts towards finding potential antiviral targets and drug development measures. While new drug discovery is time consuming, drug repurposing has been a promising area for elaborate ... ...

    Abstract

    The pandemic of SARS-CoV-2 has necessitated expedited research efforts towards finding potential antiviral targets and drug development measures. While new drug discovery is time consuming, drug repurposing has been a promising area for elaborate virtual screening and identification of existing FDA approved drugs that could possibly be used for targeting against functions of various proteins of SARS-CoV-2 virus. RNA dependent RNA polymerase (RdRp) is an important enzyme for the virus that mediates replication of the viral RNA. Inhibition of RdRp could inhibit viral RNA replication and thus new virus particle production. Here, we screened non-nucleoside antivirals and found three out of them to be strongest in binding to RdRp. We propose these three drugs as potential RdRp inhibitors based on the site of binding.


    Keywords covid19
    Publisher American Chemical Society (ACS)
    Publishing country us
    Document type Book ; Online
    DOI 10.26434/chemrxiv.12721634
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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