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  1. Article: Structure-Function Characteristics of SARS-CoV-2 Proteases and Their Potential Inhibitors from Microbial Sources.

    Razali, Rafida / Asis, Haslina / Budiman, Cahyo

    Microorganisms

    2021  Volume 9, Issue 12

    Abstract: The COVID-19 pandemic, caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is considered the greatest challenge to the global health community of the century as it continues to expand. This has prompted immediate urgency to discover ... ...

    Abstract The COVID-19 pandemic, caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is considered the greatest challenge to the global health community of the century as it continues to expand. This has prompted immediate urgency to discover promising drug targets for the treatment of COVID-19. The SARS-CoV-2 viral proteases, 3-chymotrypsin-like protease (3CLpro) and papain-like cysteine protease (PLpro), have become the promising target to study due to their essential functions in spreading the virus by RNA transcription, translation, protein synthesis, processing and modification, virus replication, and infection of the host. As such, understanding of the structure and function of these two proteases is unavoidable as platforms for the development of inhibitors targeting this protein which further arrest the infection and spread of the virus. While the abundance of reports on the screening of natural compounds such as SARS-CoV-2 proteases inhibitors are available, the microorganisms-based compounds (peptides and non-peptides) remain less studied. Indeed, microorganisms-based compounds are also one of the potent antiviral candidates against COVID-19. Microbes, especially bacteria and fungi, are other resources to produce new drugs as well as nucleosides, nucleotides, and nucleic acids. Thus, we have compiled various reported literature in detail on the structures, functions of the SARS-CoV-2 proteases, and potential inhibitors from microbial sources as assistance to other researchers working with COVID-19. The compounds are also compared to HIV protease inhibitors which suggested the microorganisms-based compounds are advantageous as SARS-CoV2 proteases inhibitors. The information should serve as a platform for further development of COVID-19 drug design strategies.
    Language English
    Publishing date 2021-11-30
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2720891-6
    ISSN 2076-2607
    ISSN 2076-2607
    DOI 10.3390/microorganisms9122481
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Heterologous Expression and Catalytic Properties of Codon-Optimized Small-Sized Bromelain from MD2 Pineapple.

    Razali, Rafida / Fahrudin, Fikran Aranda / Subbiah, Vijay Kumar / Takano, Kazufumi / Budiman, Cahyo

    Molecules (Basel, Switzerland)

    2022  Volume 27, Issue 18

    Abstract: Bromelain is a unique enzyme-based bioactive complex containing a mixture of cysteine proteases specifically found in the stems and fruits of pineapple ( ...

    Abstract Bromelain is a unique enzyme-based bioactive complex containing a mixture of cysteine proteases specifically found in the stems and fruits of pineapple (
    MeSH term(s) Ananas/chemistry ; Ananas/genetics ; Bromelains/chemistry ; Codon/genetics ; Cysteine Proteases ; Glutathione Transferase/genetics ; Urea
    Chemical Substances Codon ; Urea (8W8T17847W) ; Bromelains (9001-00-7) ; Glutathione Transferase (EC 2.5.1.18) ; Cysteine Proteases (EC 3.4.-)
    Language English
    Publishing date 2022-09-16
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 1413402-0
    ISSN 1420-3049 ; 1431-5165 ; 1420-3049
    ISSN (online) 1420-3049
    ISSN 1431-5165 ; 1420-3049
    DOI 10.3390/molecules27186031
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Technical Data of Heterologous Expression and Purification of SARS-CoV-2 Proteases Using Escherichia coli System

    Rafida Razali / Vijay Kumar Subbiah / Cahyo Budiman

    Data, Vol 6, Iss 99, p

    2021  Volume 99

    Abstract: The SARS-CoV-2 coronavirus expresses two essential proteases: firstly, the 3Chymotrypsin-like protease (3CLpro) or main protease (Mpro), and secondly, the papain-like protease (PLpro), both of which are considered as viable drug targets for the ... ...

    Abstract The SARS-CoV-2 coronavirus expresses two essential proteases: firstly, the 3Chymotrypsin-like protease (3CLpro) or main protease (Mpro), and secondly, the papain-like protease (PLpro), both of which are considered as viable drug targets for the inhibition of viral replication. In order to perform drug discovery assays for SARS-CoV-2, it is imperative that efficient methods are established for the production and purification of 3CLpro and PLpro of SARS-CoV-2, designated as 3CLpro-CoV2 and PLpro-CoV2, respectively. This article expands the data collected in the attempts to express SARS-CoV-2 proteases under different conditions and purify them under single-step chromatography. Data showed that the use of E. coli BL21(DE3) strain was sufficient to express 3CLpro-CoV2 in a fully soluble form. Nevertheless, the single affinity chromatography step was only applicable for 3CLpro-CoV2 expressed at 18 °C, with a yield and purification fold of 92% and 49, respectively. Meanwhile, PLpro-CoV2 was successfully expressed in a fully soluble form in either BL21(DE3) or BL21-CodonPlus(DE3) strains. In contrast, the single affinity chromatography step was only applicable for PLpro-CoV2 expressed using E. coli BL21-CodonPlus(DE3) at 18 or 37 °C, with a yield and purification fold of 86% (18 °C) or 83.36% (37 °C) and 112 (18 °C) or 71 (37 °C), respectively. The findings provide a guide for optimizing the production of SARS-CoV-2 proteases of E. coli host cells.
    Keywords SARS-CoV-2 proteases ; 3Chymotrypsin-like protease ; papain-like protease ; heterologous expression ; protein purification ; Bibliography. Library science. Information resources ; Z
    Subject code 572
    Language English
    Publishing date 2021-09-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article: Structure-Function Characteristics of SARS-CoV-2 Proteases and Their Potential Inhibitors from Microbial Sources

    Razali, Rafida / Asis, Haslina / Budiman, Cahyo

    Microorganisms. 2021 Nov. 30, v. 9, no. 12

    2021  

    Abstract: The COVID-19 pandemic, caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is considered the greatest challenge to the global health community of the century as it continues to expand. This has prompted immediate urgency to discover ... ...

    Abstract The COVID-19 pandemic, caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is considered the greatest challenge to the global health community of the century as it continues to expand. This has prompted immediate urgency to discover promising drug targets for the treatment of COVID-19. The SARS-CoV-2 viral proteases, 3-chymotrypsin-like protease (3CLpro) and papain-like cysteine protease (PLpro), have become the promising target to study due to their essential functions in spreading the virus by RNA transcription, translation, protein synthesis, processing and modification, virus replication, and infection of the host. As such, understanding of the structure and function of these two proteases is unavoidable as platforms for the development of inhibitors targeting this protein which further arrest the infection and spread of the virus. While the abundance of reports on the screening of natural compounds such as SARS-CoV-2 proteases inhibitors are available, the microorganisms-based compounds (peptides and non-peptides) remain less studied. Indeed, microorganisms-based compounds are also one of the potent antiviral candidates against COVID-19. Microbes, especially bacteria and fungi, are other resources to produce new drugs as well as nucleosides, nucleotides, and nucleic acids. Thus, we have compiled various reported literature in detail on the structures, functions of the SARS-CoV-2 proteases, and potential inhibitors from microbial sources as assistance to other researchers working with COVID-19. The compounds are also compared to HIV protease inhibitors which suggested the microorganisms-based compounds are advantageous as SARS-CoV2 proteases inhibitors. The information should serve as a platform for further development of COVID-19 drug design strategies.
    Keywords COVID-19 infection ; RNA ; Severe acute respiratory syndrome coronavirus 2 ; cysteine proteinases ; drug design ; nucleosides ; nucleotides ; peptides ; protein synthesis ; virus replication ; viruses
    Language English
    Dates of publication 2021-1130
    Publishing place Multidisciplinary Digital Publishing Institute
    Document type Article
    ZDB-ID 2720891-6
    ISSN 2076-2607
    ISSN 2076-2607
    DOI 10.3390/microorganisms9122481
    Database NAL-Catalogue (AGRICOLA)

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  5. Article ; Online: Soluble Expression and Catalytic Properties of Codon-Optimized Recombinant Bromelain from MD2 Pineapple in Escherichia coli.

    Razali, Rafida / Budiman, Cahyo / Kamaruzaman, Khairul Azfar / Subbiah, Vijay Kumar

    The protein journal

    2021  Volume 40, Issue 3, Page(s) 406–418

    Abstract: Bromelain, a member of cysteine proteases, is found abundantly in pineapple (Ananas comosus), and it has a myriad of versatile applications. However, attempts to produce recombinant bromelain for commercialization purposes are challenging due to its ... ...

    Abstract Bromelain, a member of cysteine proteases, is found abundantly in pineapple (Ananas comosus), and it has a myriad of versatile applications. However, attempts to produce recombinant bromelain for commercialization purposes are challenging due to its expressibility and solubility. This study aims to express recombinant fruit bromelain from MD2 pineapple (MD2Bro; accession no: OAY85858.1) in soluble and active forms using Escherichia coli host cell. The gene encoding MD2Bro was codon-optimized, synthesized, and subsequently ligated into pET-32b( +) for further transformation into Escherichia coli BL21-CodonPlus(DE3). Under this strategy, the expressed MD2Bro was in a fusion form with thioredoxin (Trx) tag at its N-terminal (Trx-MD2Bro). The result showed that Trx-MD2Bro was successfully expressed in fully soluble form. The protein was successfully purified using single-step Ni
    MeSH term(s) Ananas/enzymology ; Ananas/genetics ; Bromelains/biosynthesis ; Bromelains/chemistry ; Bromelains/genetics ; Bromelains/isolation & purification ; Catalysis ; Gene Expression ; Plant Proteins/biosynthesis ; Plant Proteins/chemistry ; Plant Proteins/genetics ; Plant Proteins/isolation & purification ; Recombinant Proteins/biosynthesis ; Recombinant Proteins/chemistry ; Recombinant Proteins/genetics ; Recombinant Proteins/isolation & purification
    Chemical Substances Plant Proteins ; Recombinant Proteins ; Bromelains (9001-00-7)
    Language English
    Publishing date 2021-03-13
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2143071-8
    ISSN 1875-8355 ; 1572-3887
    ISSN (online) 1875-8355
    ISSN 1572-3887
    DOI 10.1007/s10930-021-09974-9
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Technical Data of In Silico Analysis of the Interaction of Dietary Flavonoid Compounds against Spike-Glycoprotein and Proteases of SARS-CoV-2

    Nurbella Sofiana Altu / Cahyo Budiman / Rafida Razali / Ruzaidi Azli Mohd Mokhtar / Khairul Azfar Kamaruzaman

    Data, Vol 7, Iss 144, p

    2022  Volume 144

    Abstract: The spike glycoprotein (S protein), 3-chymotrypsin-like protease (3CL-Pro), and papain-like protease (PL-Pro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus are widely targeted for the discovery of therapeutic compounds against ... ...

    Abstract The spike glycoprotein (S protein), 3-chymotrypsin-like protease (3CL-Pro), and papain-like protease (PL-Pro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus are widely targeted for the discovery of therapeutic compounds against this virus. Dietary flavonoid compounds were proposed as a candidate for safe therapy for COVID-19 patients. Nevertheless, wet lab experiments for high-throughput screening of the compounds are undoubtedly time and cost consuming. This study aims to screen dietary flavonoid compounds that bind to S protein, 3CL-Pro, and PL-Pro of SARS-CoV-2. For this purpose, protein structures of the receptor-binding domain (RBD) of S protein (6M0J), 3CL-Pro (6LU7), and PL-Pro (6W9C) were retrieved from the RCSB Protein Data Bank (PDB). Twelve dietary flavonoid compounds were selected for the studies on their binding affinity to the targeted proteins by global and local docking. The docking and molecular dynamic (MD) simulations were performed using YASARA software. Out of 12 compounds, the highest binding score was observed between hesperidin against RBD S protein (−9.98 kcal/mol), 3CL-Pro (−9.43 kcal/mol), and PL-Pro (−8.89 kcal/mol) in global docking. Interestingly, MD simulation revealed that the complex between 3CL-Pro and RBD S protein has better stability than PL-Pro. This study suggests that hesperidin might have versatile inhibitory properties against several essential proteins of SARS-CoV-2. This study, nevertheless, remains to be confirmed through in vitro and in vivo assays.
    Keywords SARS-CoV-2 ; receptor-binding domain (RBD) of S protein ; 3-chymotrypsin-like protease (3CL-Pro) ; papain-like protease (PL-Pro) ; molecular docking and dynamic simulation ; Bibliography. Library science. Information resources ; Z
    Subject code 500
    Language English
    Publishing date 2022-10-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Technical data on the inhibition properties of some medicinal plant extracts towards caseinolytic protease proteolytic subunit of

    Razak, Raimalynah Abd / Suzery, Meiny / Razali, Rafida / Amin, Zarina / Mokhtar, Ruzaidi Azli Mohd / Lee, Ping Chin / Budiman, Cahyo

    Data in brief

    2021  Volume 39, Page(s) 107588

    Abstract: Proteolytic subunit of the caseinolytic protease system ... ...

    Abstract Proteolytic subunit of the caseinolytic protease system of
    Language English
    Publishing date 2021-11-20
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 2786545-9
    ISSN 2352-3409 ; 2352-3409
    ISSN (online) 2352-3409
    ISSN 2352-3409
    DOI 10.1016/j.dib.2021.107588
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Catalytic Properties of Caseinolytic Protease Subunit of

    Budiman, Cahyo / Razak, Raimalynah Abd / Unggit, Angelesa Runin Anak / Razali, Rafida / Suzery, Meiny / Mokhtar, Ruzaidi Azli Mohd / Lee, Ping-Chin / Utomo, Didik Huswo

    Molecules (Basel, Switzerland)

    2022  Volume 27, Issue 12

    Abstract: The caseinolytic protease (Clp) system plays an essential role in the protein homeostasis of the malaria parasite, particularly at the stage of apicoplast development. The inhibition of this protein is known to have a lethal effect on the parasite and is ...

    Abstract The caseinolytic protease (Clp) system plays an essential role in the protein homeostasis of the malaria parasite, particularly at the stage of apicoplast development. The inhibition of this protein is known to have a lethal effect on the parasite and is therefore considered an interesting avenue for antimalaria drugs discovery. The catalytic activity of the Clp system is modulated by its proteolytic subunit (ClpP), which belongs to the serine protease family member and is therefore extensively studied for further inhibitors development. Among many inhibitors, the group of β-lactone is known to be a specific inhibitor for ClpP. Nevertheless, other groups of lactones have never been studied. This study aims to characterize the catalytic properties of ClpP of
    MeSH term(s) Catalytic Domain ; Escherichia coli ; Lactones/pharmacology ; Plasmodium knowlesi ; Serine Proteases
    Chemical Substances Lactones ; Serine Proteases (EC 3.4.-)
    Language English
    Publishing date 2022-06-12
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 1413402-0
    ISSN 1420-3049 ; 1431-5165 ; 1420-3049
    ISSN (online) 1420-3049
    ISSN 1431-5165 ; 1420-3049
    DOI 10.3390/molecules27123787
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Technical data on the inhibition properties of some medicinal plant extracts towards caseinolytic protease proteolytic subunit of Plasmodium knowlesi

    Raimalynah Abd Razak / Meiny Suzery / Rafida Razali / Zarina Amin / Ruzaidi Azli Mohd Mokhtar / Ping Chin Lee / Cahyo Budiman

    Data in Brief, Vol 39, Iss , Pp 107588- (2021)

    2021  

    Abstract: Proteolytic subunit of the caseinolytic protease system of Plasmodium knowlesi (Pk-ClpP; EC 3.4.21.92) is considered a viable target for antimalarial drug development to eradicate P. knowlesi malaria infection in Malaysia and Southeast Asian region. ... ...

    Abstract Proteolytic subunit of the caseinolytic protease system of Plasmodium knowlesi (Pk-ClpP; EC 3.4.21.92) is considered a viable target for antimalarial drug development to eradicate P. knowlesi malaria infection in Malaysia and Southeast Asian region. Inhibition of this system leads to a disruption in the protein homeostasis molecular machinery and therefore be lethal for the parasite. While plants are considered excellent sources of bioactive compounds exhibiting inhibition activity towards Pk-ClpP, many local medicinal plants remain unexplored. This article expands the data collected from the inhibition properties of the methanolic extract of Asystasia gangetica (Chinese Violet), Alstonia scholaris (Pulai Tree), Piper retrofractum (Javanese Long Pepper) and Smallanthus sonchifolius (Yacon) towards Pk-ClpP. These plants are widely found in Malaysia and Indonesia and have been traditionally used in various medical treatments. The present dataset showed that the extracts contained phenolic and flavonoid compounds in various concentrations, whereby S. sonchifolius was found to have the lowest content of phenolic and flavonoid contents, while A. gangetica and A. scholaris were statistically comparable, yet higher than P. retrofactum and S. sonchifolus. Further inhibition data assay towards Pk-ClpP revealed that A. gangetica, A. scholaris and P. retrofactum demonstrated remarkable inhibition activity with IC50 values of 39.06 ± 1.98, 48.92 ± 1.52, and 87.63 ± 3.55, respectively. However, the inhibition activity of these extracts was significantly lower than a serine protease inhibitor of phenylmethylsulfonyl fluoridenone (PMSF). Meanwhile, S. sonchifolus did not exhibit significant inhibition activity towards Pk-ClpP. In addition, Pk-ClpP was not inhibited by a cysteine protease inhibitor of E64.
    Keywords Plasmodium knowlesi ; Malaria ; Caseinolytic protease ; Plant extracts ; Computer applications to medicine. Medical informatics ; R858-859.7 ; Science (General) ; Q1-390
    Subject code 572
    Language English
    Publishing date 2021-12-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article: Technical data on the inhibition properties of some medicinal plant extracts towards caseinolytic protease proteolytic subunit of Plasmodium knowlesi

    Razak, Raimalynah Abd / Suzery, Meiny / Razali, Rafida / Amin, Zarina / Mokhtar, Ruzaidi Azli Mohd / Lee, Ping Chin / Budiman, Cahyo

    Data in Brief. 2021 Dec., v. 39

    2021  

    Abstract: Proteolytic subunit of the caseinolytic protease system of Plasmodium knowlesi (Pk-ClpP; EC 3.4.21.92) is considered a viable target for antimalarial drug development to eradicate P. knowlesi malaria infection in Malaysia and Southeast Asian region. ... ...

    Abstract Proteolytic subunit of the caseinolytic protease system of Plasmodium knowlesi (Pk-ClpP; EC 3.4.21.92) is considered a viable target for antimalarial drug development to eradicate P. knowlesi malaria infection in Malaysia and Southeast Asian region. Inhibition of this system leads to a disruption in the protein homeostasis molecular machinery and therefore be lethal for the parasite. While plants are considered excellent sources of bioactive compounds exhibiting inhibition activity towards Pk-ClpP, many local medicinal plants remain unexplored. This article expands the data collected from the inhibition properties of the methanolic extract of Asystasia gangetica (Chinese Violet), Alstonia scholaris (Pulai Tree), Piper retrofractum (Javanese Long Pepper) and Smallanthus sonchifolius (Yacon) towards Pk-ClpP. These plants are widely found in Malaysia and Indonesia and have been traditionally used in various medical treatments. The present dataset showed that the extracts contained phenolic and flavonoid compounds in various concentrations, whereby S. sonchifolius was found to have the lowest content of phenolic and flavonoid contents, while A. gangetica and A. scholaris were statistically comparable, yet higher than P. retrofactum and S. sonchifolus. Further inhibition data assay towards Pk-ClpP revealed that A. gangetica, A. scholaris and P. retrofactum demonstrated remarkable inhibition activity with IC₅₀ values of 39.06 ± 1.98, 48.92 ± 1.52, and 87.63 ± 3.55, respectively. However, the inhibition activity of these extracts was significantly lower than a serine protease inhibitor of phenylmethylsulfonyl fluoridenone (PMSF). Meanwhile, S. sonchifolus did not exhibit significant inhibition activity towards Pk-ClpP. In addition, Pk-ClpP was not inhibited by a cysteine protease inhibitor of E64.
    Keywords Alstonia scholaris ; Asystasia gangetica ; Piper longum ; Piper retrofractum ; Plasmodium knowlesi ; Smallanthus sonchifolius ; antimalarials ; cysteine proteinase inhibitors ; data collection ; drug development ; flavonoids ; homeostasis ; malaria ; medicinal plants ; parasites ; proteolysis ; serine proteinases ; Indonesia ; Malaysia
    Language English
    Dates of publication 2021-12
    Publishing place Elsevier Inc.
    Document type Article
    ZDB-ID 2786545-9
    ISSN 2352-3409
    ISSN 2352-3409
    DOI 10.1016/j.dib.2021.107588
    Database NAL-Catalogue (AGRICOLA)

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