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  1. Article ; Online: Human SARS CoV-2 spike protein mutations.

    Guruprasad, Lalitha

    Proteins

    2021  Volume 89, Issue 5, Page(s) 569–576

    Abstract: The human spike protein sequences from Asia, Africa, Europe, North America, South America, and Oceania were analyzed by comparing with the reference severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) protein sequence from Wuhan-Hu-1, China. Out ...

    Abstract The human spike protein sequences from Asia, Africa, Europe, North America, South America, and Oceania were analyzed by comparing with the reference severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) protein sequence from Wuhan-Hu-1, China. Out of 10333 spike protein sequences analyzed, 8155 proteins comprised one or more mutations. A total of 9654 mutations were observed that correspond to 400 distinct mutation sites. The receptor binding domain (RBD) which is involved in the interactions with human angiotensin-converting enzyme-2 (ACE-2) receptor and causes infection leading to the COVID-19 disease comprised 44 mutations that included residues within 3.2 Å interacting distance from the ACE-2 receptor. The mutations observed in the spike proteins are discussed in the context of their distribution according to the geographical locations, mutation sites, mutation types, distribution of the number of mutations at the mutation sites and mutations at the glycosylation sites. The density of mutations in different regions of the spike protein sequence and location of the mutations in protein three-dimensional structure corresponding to the RBD are discussed. The mutations identified in the present work are important considerations for antibody, vaccine, and drug development.
    MeSH term(s) Humans ; Mutation ; Spike Glycoprotein, Coronavirus/genetics
    Chemical Substances Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2
    Language English
    Publishing date 2021-01-17
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 806683-8
    ISSN 1097-0134 ; 0887-3585
    ISSN (online) 1097-0134
    ISSN 0887-3585
    DOI 10.1002/prot.26042
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Human coronavirus spike protein-host receptor recognition.

    Guruprasad, Lalitha

    Progress in biophysics and molecular biology

    2020  Volume 161, Page(s) 39–53

    Abstract: A variety of coronaviruses (CoVs) have infected humans and caused mild to severe respiratory diseases that could result in mortality. The human CoVs (HCoVs) belong to the genera of α- and β-CoVs that originate in rodents and bats and are transmitted to ... ...

    Abstract A variety of coronaviruses (CoVs) have infected humans and caused mild to severe respiratory diseases that could result in mortality. The human CoVs (HCoVs) belong to the genera of α- and β-CoVs that originate in rodents and bats and are transmitted to humans via zoonotic contacts. The binding of viral spike proteins to the host cell receptors is essential for mediating fusion of viral and host cell membranes to cause infection. The SARS-CoV-2 originated in bats (RaTG13 SARS-CoV) and is transmitted to humans via pangolins. The presence of 'PRRA' sequence motif in SARS-CoV-2 spike proteins from human, dog, cat, mink, tiger and lion suggests a common viral entry mechanism into host cells. In this review, we discuss structural features of HCoV spike proteins and recognition of host protein and carbohydrate receptors.
    MeSH term(s) Amino Acid Motifs ; Animals ; COVID-19/immunology ; Carbohydrates/chemistry ; Chiroptera ; Cryoelectron Microscopy ; Databases, Protein ; Drug Repositioning ; Genome, Viral ; Humans ; Middle East Respiratory Syndrome Coronavirus ; Pangolins ; Phylogeny ; Protein Binding ; Protein Conformation ; Protein Interaction Mapping ; Receptors, Virus/chemistry ; SARS-CoV-2 ; Species Specificity ; Spike Glycoprotein, Coronavirus/chemistry
    Chemical Substances Carbohydrates ; Receptors, Virus ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2
    Keywords covid19
    Language English
    Publishing date 2020-10-31
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 209302-9
    ISSN 1873-1732 ; 0079-6107
    ISSN (online) 1873-1732
    ISSN 0079-6107
    DOI 10.1016/j.pbiomolbio.2020.10.006
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Evolutionary relationships and sequence-structure determinants in human SARS coronavirus-2 spike proteins for host receptor recognition.

    Guruprasad, Lalitha

    Proteins

    2020  Volume 88, Issue 11, Page(s) 1387–1393

    Abstract: Coronavirus disease 2019 (COVID-19) is a pandemic infectious disease caused by novel severe acute respiratory syndrome coronavirus-2 (SARS CoV-2). The SARS CoV-2 is transmitted more rapidly and readily than SARS CoV. Both, SARS CoV and SARS CoV-2 via ... ...

    Abstract Coronavirus disease 2019 (COVID-19) is a pandemic infectious disease caused by novel severe acute respiratory syndrome coronavirus-2 (SARS CoV-2). The SARS CoV-2 is transmitted more rapidly and readily than SARS CoV. Both, SARS CoV and SARS CoV-2 via their glycosylated spike proteins recognize the human angiotensin converting enzyme-2 (ACE-2) receptor. We generated multiple sequence alignments and phylogenetic trees for representative spike proteins of SARS CoV and SARS CoV-2 from various host sources in order to analyze the specificity in SARS CoV-2 spike proteins required for causing infection in humans. Our results show that among the genomes analyzed, two sequence regions in the N-terminal domain "MESEFR" and "SYLTPG" are specific to human SARS CoV-2. In the receptor-binding domain, two sequence regions "VGGNY" and "EIYQAGSTPCNGV" and a disulfide bridge connecting 480C and 488C in the extended loop are structural determinants for the recognition of human ACE-2 receptor. The complete genome analysis of representative SARS CoVs from bat, civet, human host sources, and human SARS CoV-2 identified the bat genome (GenBank code: MN996532.1) as closest to the recent novel human SARS CoV-2 genomes. The bat SARS CoV genomes (GenBank codes: MG772933 and MG772934) are evolutionary intermediates in the mutagenesis progression toward becoming human SARS CoV-2.
    MeSH term(s) Angiotensin-Converting Enzyme 2 ; Animals ; Betacoronavirus/chemistry ; Betacoronavirus/genetics ; Betacoronavirus/metabolism ; Binding Sites ; Chiroptera/virology ; Disulfides/chemistry ; Evolution, Molecular ; Host-Pathogen Interactions/physiology ; Humans ; Peptidyl-Dipeptidase A/metabolism ; Phylogeny ; SARS-CoV-2 ; Sequence Alignment ; Spike Glycoprotein, Coronavirus/chemistry ; Spike Glycoprotein, Coronavirus/metabolism
    Chemical Substances Disulfides ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2 ; Peptidyl-Dipeptidase A (EC 3.4.15.1) ; ACE2 protein, human (EC 3.4.17.23) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23)
    Keywords covid19
    Language English
    Publishing date 2020-07-04
    Publishing country United States
    Document type Journal Article
    ZDB-ID 806683-8
    ISSN 1097-0134 ; 0887-3585
    ISSN (online) 1097-0134
    ISSN 0887-3585
    DOI 10.1002/prot.25967
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Computational studies on the design of NCI natural products as inhibitors to SARS-CoV-2 main protease.

    Durgam, Laxman / Guruprasad, Lalitha

    Journal of biomolecular structure & dynamics

    2022  Volume 41, Issue 9, Page(s) 3741–3751

    Abstract: The pandemic coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in more than 5 million deaths globally. Currently there are no effective drugs available to treat COVID-19. The viral protease ...

    Abstract The pandemic coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in more than 5 million deaths globally. Currently there are no effective drugs available to treat COVID-19. The viral protease replication can be blocked by the inhibition of main protease that is encoded in polyprotein 1a and is therefore a potential protein target for drug discovery. We have carried out virtual screening of NCI natural compounds followed by molecular docking in order to identify hit molecules as probable SARS-CoV-2 main protease inhibitors. The molecular dynamics (MD) simulations of apo form in complex with N3, α-ketoamide and NCI natural products was used to validate the screened compounds. The MD simulations trajectories were analyzed using normal mode analysis and principal component analysis revealing dynamical nature of the protein. These findings aid in understanding the binding of natural products and molecular mechanisms of SARS-CoV-2 main protease inhibition.Communicated by Ramaswamy H. Sarma.
    MeSH term(s) Humans ; COVID-19 ; Molecular Docking Simulation ; SARS-CoV-2 ; Biological Products/pharmacology ; Molecular Dynamics Simulation ; Peptide Hydrolases ; Protease Inhibitors/pharmacology
    Chemical Substances 3C-like proteinase, SARS-CoV-2 (EC 3.4.22.-) ; Biological Products ; Peptide Hydrolases (EC 3.4.-) ; Protease Inhibitors
    Language English
    Publishing date 2022-03-25
    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 10.1080/07391102.2022.2054470
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Evolutionary relationships and sequence-structure determinants in human SARS coronavirus-2 spike proteins for host receptor recognition

    Guruprasad, Lalitha

    Proteins

    Abstract: Coronavirus disease 2019 (COVID-19) is a pandemic infectious disease caused by novel severe acute respiratory syndrome coronavirus-2 (SARS CoV-2). The SARS CoV-2 is transmitted more rapidly and readily than SARS CoV. Both, SARS CoV and SARS CoV-2 via ... ...

    Abstract Coronavirus disease 2019 (COVID-19) is a pandemic infectious disease caused by novel severe acute respiratory syndrome coronavirus-2 (SARS CoV-2). The SARS CoV-2 is transmitted more rapidly and readily than SARS CoV. Both, SARS CoV and SARS CoV-2 via their glycosylated spike proteins recognize the human angiotensin converting enzyme-2 (ACE-2) receptor. We generated multiple sequence alignments and phylogenetic trees for representative spike proteins of SARS CoV and SARS CoV-2 from various host sources in order to analyze the specificity in SARS CoV-2 spike proteins required for causing infection in humans. Our results show that among the genomes analyzed, two sequence regions in the N-terminal domain "MESEFR" and "SYLTPG" are specific to human SARS CoV-2. In the receptor-binding domain, two sequence regions "VGGNY" and "EIYQAGSTPCNGV" and a disulfide bridge connecting 480C and 488C in the extended loop are structural determinants for the recognition of human ACE-2 receptor. The complete genome analysis of representative SARS CoVs from bat, civet, human host sources, and human SARS CoV-2 identified the bat genome (GenBank code: MN996532.1) as closest to the recent novel human SARS CoV-2 genomes. The bat SARS CoV genomes (GenBank codes: MG772933 and MG772934) are evolutionary intermediates in the mutagenesis progression toward becoming human SARS CoV-2.
    Keywords covid19
    Publisher WHO
    Document type Article
    Note WHO #Covidence: #599391
    Database COVID19

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  6. Article: Human coronavirus spike protein-host receptor recognition

    Guruprasad, Lalitha

    Prog. biophys. mol. biol

    Abstract: A variety of coronaviruses (CoVs) have infected humans and caused mild to severe respiratory diseases that could result in mortality. The human CoVs (HCoVs) belong to the genera of α- and ß-CoVs that originate in rodents and bats and are transmitted to ... ...

    Abstract A variety of coronaviruses (CoVs) have infected humans and caused mild to severe respiratory diseases that could result in mortality. The human CoVs (HCoVs) belong to the genera of α- and ß-CoVs that originate in rodents and bats and are transmitted to humans via zoonotic contacts. The binding of viral spike proteins to the host cell receptors is essential for mediating fusion of viral and host cell membranes to cause infection. In this review, we discuss structural features of HCoV spike proteins and recognition of host proteins and carbohydrate receptors.
    Keywords covid19
    Publisher WHO
    Document type Article
    Note WHO #Covidence: #894160
    Database COVID19

    Kategorien

  7. Book ; Online: HUMAN SARS CoV-2 SPIKE PROTEIN MUTATIONS

    Guruprasad, Lalitha

    2020  

    Abstract: ... The human SARS-CoV-2 spike protein sequences from Asia, Africa, Europe, North America, South America and Oceania were analyzed by comparing with the reference SARS-CoV-2 protein sequence from Wuhan-Hu-1, China. Out of 10,333 spike protein sequences ... ...

    Abstract

    The human SARS-CoV-2 spike protein sequences from Asia, Africa, Europe, North America, South America and Oceania were analyzed by comparing with the reference SARS-CoV-2 protein sequence from Wuhan-Hu-1, China. Out of 10,333 spike protein sequences analyzed, 8,155 proteins comprised one or more mutations. A total of 9,654 mutations were observed that correspond to 400 distinct mutation sites. The receptor binding domain (RBD) which is involved in the interactions with human ACE-2 receptor and causes infection leading to the COVID-19 disease comprised 44 mutations that included residues within 3.2 Å interacting distance from the ACE-2 receptor. The mutations observed in the spike proteins are discussed in the context of their distribution according to the geographical locations, mutation sites, mutation types, distribution of the number of mutations at the mutation sites and mutations at the glycosylation sites. The density of mutations in different regions of the spike protein sequence and location of the mutations in protein three-dimensional structure corresponding to the RBD are discussed. The mutations identified in the present work are important considerations for antibody, vaccine and drug development.


    Keywords covid19
    Publisher American Chemical Society (ACS)
    Publishing country us
    Document type Book ; Online
    DOI 10.26434/chemrxiv.12827966
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Book ; Online: HUMAN SARS CoV-2 SPIKE PROTEIN MUTATIONS

    Guruprasad, Lalitha

    2020  

    Abstract: ... The human SARS-CoV-2 spike protein sequences from Asia, Africa, Europe, North America, South America and Oceania were analyzed by comparing with the reference SARS-CoV-2 protein sequence from Wuhan-Hu-1, China. Out of 10,333 spike protein sequences ... ...

    Abstract

    The human SARS-CoV-2 spike protein sequences from Asia, Africa, Europe, North America, South America and Oceania were analyzed by comparing with the reference SARS-CoV-2 protein sequence from Wuhan-Hu-1, China. Out of 10,333 spike protein sequences analyzed, 8,155 proteins comprised one or more mutations. A total of 9,654 mutations were observed that correspond to 400 distinct mutation sites. The receptor binding domain (RBD) which is involved in the interactions with human ACE-2 receptor and causes infection leading to the COVID-19 disease comprised 44 mutations that included residues within 3.2 Å interacting distance from the ACE-2 receptor. The mutations observed in the spike proteins are discussed in the context of their distribution according to the geographical locations, mutation sites, mutation types, distribution of the number of mutations at the mutation sites and mutations at the glycosylation sites. The density of mutations in different regions of the spike protein sequence and location of the mutations in protein three-dimensional structure corresponding to the RBD are discussed. The mutations identified in the present work are important considerations for antibody, vaccine and drug development.


    Keywords covid19
    Publisher American Chemical Society (ACS)
    Publishing country us
    Document type Book ; Online
    DOI 10.26434/chemrxiv.12827966.v1
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    More links

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  9. Book ; Online: Evolutionary Relationships and Sequence-Structure Determinants in Human SARS Coronavirus-2 Spike Proteins for Host Receptor Recognition

    Guruprasad, Lalitha

    2020  

    Abstract: ... Coronavirus disease 2019 (COVID-19) is a pandemic infectious disease caused by novel Severe Acute Respiratory Syndrome coronavirus-2 (SARS CoV-2). The SARS CoV-2 is transmitted more rapidly and readily than SARS CoV. Both, SARS CoV and SARS CoV-2 ... ...

    Abstract
    Coronavirus disease 2019 (COVID-19) is a pandemic infectious disease caused by novel Severe Acute Respiratory Syndrome coronavirus-2 (SARS CoV-2). The SARS CoV-2 is transmitted more rapidly and readily than SARS CoV. Both, SARS CoV and SARS CoV-2 via their glycosylated spike proteins recognize the human angiotensin converting enzyme-2 (ACE-2) receptor. We generated multiple sequence alignments and phylogenetic trees for representative spike proteins of CoV and CoV-2 from various host sources in order to analyze the specificity in SARS CoV-2 spike proteins required for causing infection in humans. Our results show that two sequence motifs in the N-terminal domain; "MESEFR" and "SYLTPG" are specific to human SARS CoV-2. In the receptor binding domain (RBD), two sequence motifs; "VGGNY" and "EIYQAGSTPCNGV" and a disulfide bridge connecting 480C and 488C in the extended loop are structural determinants for the recognition of human ACE-2 receptor. The complete genome analysis of representative SARS CoVs from bat, civet, human host sources and human SARS CoV-2 identified the bat genome (GenBank code: MN996532.1) as closest to the recent novel human SARS CoV-2 genomes. The bat CoV genomes (GenBank codes: MG772933 and MG772934) are evolutionary intermediates in the mutagenesis progression towards becoming human SARS CoV-2.

    Keywords covid19
    Publisher American Chemical Society (ACS)
    Publishing country us
    Document type Book ; Online
    DOI 10.26434/chemrxiv.12190449.v1
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    More links

    Kategorien

  10. Book ; Online: Evolutionary Relationships and Sequence-Structure Determinants in Human SARS Coronavirus-2 Spike Proteins for Host Receptor Recognition

    Guruprasad, Lalitha

    2020  

    Abstract: ... Coronavirus disease 2019 (COVID-19) is a pandemic infectious disease caused by novel Severe Acute Respiratory Syndrome coronavirus-2 (SARS CoV-2). The SARS CoV-2 is transmitted more rapidly and readily than SARS CoV. Both, SARS CoV and SARS CoV-2 ... ...

    Abstract
    Coronavirus disease 2019 (COVID-19) is a pandemic infectious disease caused by novel Severe Acute Respiratory Syndrome coronavirus-2 (SARS CoV-2). The SARS CoV-2 is transmitted more rapidly and readily than SARS CoV. Both, SARS CoV and SARS CoV-2 via their glycosylated spike proteins recognize the human angiotensin converting enzyme-2 (ACE-2) receptor. We generated multiple sequence alignments and phylogenetic trees for representative spike proteins of CoV and CoV-2 from various host sources in order to analyze the specificity in SARS CoV-2 spike proteins required for causing infection in humans. Our results show that two sequence motifs in the N-terminal domain; "MESEFR" and "SYLTPG" are specific to human SARS CoV-2 and pangolin SARS CoV. In the receptor binding domain (RBD), three sequence loops; VGGNY (loop 1), YQAGSTPC (loop 2), EGFNCY (loop 3) and a tethered disulfide bridge Cys480-Cys488 connecting loops 2 and 3 are structural determinants for the recognition of human ACE-2 receptor. The complete genome analysis of representative SARS CoVs from bat, civet, pangolin, human host sources and human SARS CoV-2 identified the bat genome (GenBank code: MN996532.1) and the pangolin SARS CoV genomes as closest to the recent novel human SARS CoV-2 genomes. The bat CoV genomes (GenBank codes: MG772933 and MG772934) are evolutionary intermediates in the mutagenesis progression towards becoming human SARS CoV-2.

    Keywords covid19
    Publisher American Chemical Society (ACS)
    Publishing country us
    Document type Book ; Online
    DOI 10.26434/chemrxiv.12190449
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    More links

    Kategorien

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