LIVIVO - Search results -

Search results

Result 1 - 10 of total 24

Search options

Article ; Online: Mechanisms of residual immune activation in HIV-1-infected human lymphoid tissue ex vivo.

Mercurio, Vincenzo / Fitzgerald, Wendy / Vanpouille, Christophe / Molodtsov, Ivan / Margolis, Leonid

2021 Volume 35, Issue 8, Page(s) 1179–1190

Abstract: Objective: HIV-1 infection triggers immune activation, as reflected by the upregulation of various cytokines. This immune activation remains elevated despite antiretroviral therapy (ART) and leads to early age-related diseases. Here, we addressed the ... ...

Abstract	Objective: HIV-1 infection triggers immune activation, as reflected by the upregulation of various cytokines. This immune activation remains elevated despite antiretroviral therapy (ART) and leads to early age-related diseases. Here, we addressed the mechanisms of sustained immune activation in HIV-1-infected human lymphoid tissues ex vivo. Design/method: We investigated several potential causes of immunoactivation, including: a proinflammatory effect of ART drugs themselves; an early HIV-1-triggered cytokine storm, which could in turn trigger a sustained cytokine dysregulation; herpesvirus reactivation; HIV-1 protein release; and production of defective virions and extracellular vesicles. Tissue immune activation was evaluated from measurements of cytokines in culture medium using multiplexed immunoassays. Results: Neither ART itself nor simulated cytokine storms nor exogenously added HIV-1 proteins triggered a sustained cytokine upregulation. In contrast, defective (replicative-incompetent) virions and extracellular vesicles induced sustained cytokine upregulation, as did infectious virus. Tissue immune activation was accompanied by reactivation of cytomegalovirus. Conclusion: The system of ex-vivo human lymphoid tissue allowed investigation, under laboratory-controlled conditions, of possible mechanisms involved in persistent immune activation in HIV-1 patients under ART. Mechanisms of this immunoactivation identified in ex-vivo tissues may indicate potential therapeutic targets for restoration of immune system homeostasis in HIV-1-infected patients.
MeSH term(s)	CD4-Positive T-Lymphocytes ; Cytomegalovirus ; HIV Infections/drug therapy ; HIV Seropositivity ; HIV-1 ; Humans ; Lymphoid Tissue
Language	English
Publishing date	2021-02-23
Publishing country	England
Document type	Journal Article
ZDB-ID	639076-6
ISSN	1473-5571 ; 0269-9370 ; 1350-2840
ISSN (online)	1473-5571
ISSN	0269-9370 ; 1350-2840
DOI	10.1097/QAD.0000000000002881
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 2228: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Persistent Immune Activation in HIV-1-Infected Ex Vivo Model Tissues Subjected to Antiretroviral Therapy: Soluble and Extracellular Vesicle-Associated Cytokines.

Mercurio, Vincenzo / Fitzgerald, Wendy / Molodtsov, Ivan / Margolis, Leonid

Journal of acquired immune deficiency syndromes (1999)

2020 Volume 84, Issue 1, Page(s) 45–53

Abstract: Background: Residual immune activation after successful antiretroviral therapy (ART) in HIV-1-infected patients is associated with the increased risk of complications. Cytokines, both soluble and extracellular vesicle (EV)-associated, may play an ... ...

Abstract	Background: Residual immune activation after successful antiretroviral therapy (ART) in HIV-1-infected patients is associated with the increased risk of complications. Cytokines, both soluble and extracellular vesicle (EV)-associated, may play an important role in this immune activation. Setting: Ex vivo tissues were infected with X4LAI04 or R5SF162 HIV-1. Virus replicated for 16 days, or tissues were treated with the anti-retroviral drug ritonavir. Methods: Viral replication and production of 33 cytokines in soluble and EV-associated forms were measured with multiplexed bead-based assays. Results: Both variants of HIV-1 efficiently replicated in tissues and triggered upregulation of soluble cytokines, including IL-1β, IL-7, IL-18, IFN-γ, MIP-1α, MIP-1β, and RANTES. A similar pattern was observed in EV-associated cytokine release by HIV-infected tissues. In addition, TNF-α and RANTES demonstrated a significant shift to a more soluble form compared with EV-associated cytokines. Ritonavir treatment efficiently suppressed viral replication; however, both soluble and EV-associated cytokines remained largely upregulated after 13 days of treatment. EV-associated cytokines were more likely to remain elevated after ART. Treatment of uninfected tissues with ritonavir itself did not affect cytokine release. Conclusions: We demonstrated that HIV-1 infection of ex vivo lymphoid tissues resulted in their immune activation as evaluated by upregulation of various cytokines, both soluble and EV-associated. This upregulation persisted despite inhibition of viral replication by ART. Thus, similar to in vivo, HIV-1-infected human tissues ex vivo continue to be immune-activated after viral suppression, providing a new laboratory model to study this phenomenon.
MeSH term(s)	Anti-HIV Agents/therapeutic use ; Cytokines/physiology ; Extracellular Vesicles/metabolism ; HIV Infections/drug therapy ; HIV Infections/immunology ; HIV-1 ; Humans
Chemical Substances	Anti-HIV Agents ; Cytokines
Language	English
Publishing date	2020-02-06
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Intramural
ZDB-ID	645053-2
ISSN	1944-7884 ; 1077-9450 ; 0897-5965 ; 0894-9255 ; 1525-4135
ISSN (online)	1944-7884 ; 1077-9450
ISSN	0897-5965 ; 0894-9255 ; 1525-4135
DOI	10.1097/QAI.0000000000002301
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 2442: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article: Modeling SARS-CoV-2 spike/ACE2 protein-protein interactions for predicting the binding affinity of new spike variants for ACE2, and novel ACE2 structurally related human protein targets, for COVID-19 handling in the 3PM context.

Tragni, Vincenzo / Preziusi, Francesca / Laera, Luna / Onofrio, Angelo / Mercurio, Ivan / Todisco, Simona / Volpicella, Mariateresa / De Grassi, Anna / Pierri, Ciro Leonardo

The EPMA journal

2022 Volume 13, Issue 1, Page(s) 149–175

Abstract: Aims: The rapid spread of new SARS-CoV-2 variants has highlighted the crucial role played in the infection by mutations occurring at the SARS-CoV-2 spike receptor binding domain (RBD) in the interactions with the human ACE2 receptor. In this context, it ...

Abstract	Aims: The rapid spread of new SARS-CoV-2 variants has highlighted the crucial role played in the infection by mutations occurring at the SARS-CoV-2 spike receptor binding domain (RBD) in the interactions with the human ACE2 receptor. In this context, it urgently needs to develop new rapid tools for quickly predicting the affinity of ACE2 for the SARS-CoV-2 spike RBD protein variants to be used with the ongoing SARS-CoV-2 genomic sequencing activities in the clinics, aiming to gain clues about the transmissibility and virulence of new variants, to prevent new outbreaks and to quickly estimate the severity of the disease in the context of the 3PM. Methods: In our study, we used a computational pipeline for calculating the interaction energies at the SARS-CoV-2 spike RBD/ACE2 protein-protein interface for a selected group of characterized infectious variants of concern/interest (VoC/VoI). By using our pipeline, we built 3D comparative models of the SARS-CoV-2 spike RBD/ACE2 protein complexes for the VoC B.1.1.7-United Kingdom (carrying the mutations of concern/interest N501Y, S494P, E484K at the RBD), P.1-Japan/Brazil (RBD mutations: K417T, E484K, N501Y), B.1.351-South Africa (RBD mutations: K417N, E484K, N501Y), B.1.427/B.1.429-California (RBD mutations: L452R), the B.1.141 (RBD mutations: N439K), and the recent B.1.617.1-India (RBD mutations: L452R; E484Q) and the B.1.620 (RBD mutations: S477N; E484K). Then, we used the obtained 3D comparative models of the SARS-CoV-2 spike RBD/ACE2 protein complexes for predicting the interaction energies at the protein-protein interface. Results: Along SARS-CoV-2 mutation database screening and mutation localization analysis, it was ascertained that the most dangerous mutations at VoC/VoI spike proteins are located mainly at three regions of the SARS-CoV-2 spike "boat-shaped" receptor binding motif, on the RBD domain. Notably, the P.1 Japan/Brazil variant present three mutations, K417T, E484K, N501Y, located along the entire receptor binding motif, which apparently determines the highest interaction energy at the SARS-CoV-2 spike RBD/ACE2 protein-protein interface, among those calculated. Conversely, it was also observed that the replacement of a single acidic/hydrophilic residue with a basic residue (E484K or N439K) at the "stern" or "bow" regions, of the boat-shaped receptor binding motif on the RBD, appears to determine an interaction energy with ACE2 receptor higher than that observed with single mutations occurring at the "hull" region or with other multiple mutants. In addition, our pipeline allowed searching for ACE2 structurally related proteins, i.e., THOP1 and NLN, which deserve to be investigated for their possible involvement in interactions with the SARS-CoV-2 spike protein, in those tissues showing a low expression of ACE2, or as a novel receptor for future spike variants. A freely available web-tool for the in silico calculation of the interaction energy at the SARS-CoV-2 spike RBD/ACE2 protein-protein interface, starting from the sequences of the investigated spike and/or ACE2 variants, was made available for the scientific community at: https://www.mitoairm.it/covid19affinities. Conclusion: In the context of the PPPM/3PM, the employment of the described pipeline through the provided webservice, together with the ongoing SARS-CoV-2 genomic sequencing, would help to predict the transmissibility of new variants sequenced from future patients, depending on SARS-CoV-2 genomic sequencing activities and on the specific amino acid replacement and/or on its location on the SARS-CoV-2 spike RBD, to put in play all the possible counteractions for preventing the most deleterious scenarios of new outbreaks, taking into consideration that a greater transmissibility has not to be necessarily related to a more severe manifestation of the disease. Supplementary information: The online version contains supplementary material available at 10.1007/s13167-021-00267-w.
Language	English
Publishing date	2022-01-06
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2545928-4
ISSN	1878-5085 ; 1878-5077
ISSN (online)	1878-5085
ISSN	1878-5077
DOI	10.1007/s13167-021-00267-w
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

Order via subito

Details ▾
- Full text online
- Order with fees

Article ; Online: A conformational rearrangement of the SARS-CoV-2 host protein sigma-1 is required for antiviral activity: insights from a combined in-silico/in-vitro approach.

Abatematteo, Francesca Serena / Delre, Pietro / Mercurio, Ivan / Rezelj, Veronica V / Siliqi, Dritan / Beaucourt, Stephanie / Lattanzi, Gianluca / Colabufo, Nicola Antonio / Leopoldo, Marcello / Saviano, Michele / Vignuzzi, Marco / Mangiatordi, Giuseppe Felice / Abate, Carmen

Scientific reports

2023 Volume 13, Issue 1, Page(s) 12798

Abstract: The development of effective drugs to treat coronavirus infections remains a significant challenge for the scientific community. Recent evidence reports on the sigma-1 receptor (S1R) as a key druggable host protein in the SARS-CoV-1 and SARS-CoV-2 ... ...

Abstract	The development of effective drugs to treat coronavirus infections remains a significant challenge for the scientific community. Recent evidence reports on the sigma-1 receptor (S1R) as a key druggable host protein in the SARS-CoV-1 and SARS-CoV-2 interactomes and shows a potent antiviral activity against SARS-CoV-2 for the S1R antagonist PB28. To improve PB28 activity, we designed and tested a series of its analogues and identified a compound that is fourfold more potent against SARS-CoV-2 than PB28 itself. Interestingly, we found no direct correlation between S1R affinity and SARS-CoV-2 antiviral activity. Building on this, we employed comparative induced fit docking and molecular dynamics simulations to gain insights into the possible mechanism that occurs when specific ligand-protein interactions take place and that may be responsible for the observed antiviral activity. Our findings offer a possible explanation for the experimental observations, provide insights into the S1R conformational changes upon ligand binding and lay the foundation for the rational design of new S1R ligands with potent antiviral activity against SARS-CoV-2 and likely other viruses.
MeSH term(s)	Humans ; SARS-CoV-2/metabolism ; Antiviral Agents/chemistry ; COVID-19 ; Ligands ; Molecular Dynamics Simulation ; Molecular Docking Simulation
Chemical Substances	Antiviral Agents ; Ligands
Language	English
Publishing date	2023-08-07
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-39662-w
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Deconstructing SARS-CoV-2 neutralization: A modular molecular framework for computational design and comparison of antibodies and nanobodies targeting the spike RBD.

Tragni, Vincenzo / Mercurio, Ivan / Paoletti, Diletta Pia / Onofrio, Angelo / Laera, Luna / Cafferati Beltrame, Lucas / Sgobba, Maria Noemi / Guerra, Lorenzo / Volpicella, Mariateresa / De Grassi, Anna / Elia, Gabriella / Pierri, Ciro Leonardo

Journal of medical virology

2023 Volume 95, Issue 6, Page(s) e28875

Abstract: Since 2020 the COVID-19 pandemic has led scientists to search for strategies to predict the transmissibility and virulence of new severe acute respiratory syndrome coronavirus 2 variants based on the estimation of the affinity of the spike receptor ... ...

Abstract	Since 2020 the COVID-19 pandemic has led scientists to search for strategies to predict the transmissibility and virulence of new severe acute respiratory syndrome coronavirus 2 variants based on the estimation of the affinity of the spike receptor binding domain (RBD) for the human angiotensin-converting enzyme 2 (ACE2) receptor and/or neutralizing antibodies. In this context, our lab developed a computational pipeline to quickly quantify the free energy of interaction at the spike RBD/ACE2 protein-protein interface, reflecting the incidence trend observed in the transmissibility/virulence of the investigated variants. In this new study, we used our pipeline to estimate the free energy of interaction between the RBD from 10 variants, and 14 antibodies (ab), or 5 nanobodies (nb), highlighting the RBD regions preferentially targeted by the investigated ab/nb. Our structural comparative analysis and interaction energy calculations allowed us to propose the most promising RBD regions to be targeted by future ab/nb to be designed by site-directed mutagenesis of existing high-affinity ab/nb, to increase their affinity for the target RBD region, for preventing spike-RBD/ACE2 interactions and virus entry in host cells. Furthermore, we evaluated the ability of the investigated ab/nb to simultaneously interact with the three RBD located on the surface of the trimeric spike protein, which can alternatively be in up- or down- (all-3-up-, all-3-down-, 1-up-/2-down-, 2-up-/1-down-) conformations.
MeSH term(s)	Humans ; SARS-CoV-2/genetics ; Angiotensin-Converting Enzyme 2 ; Single-Domain Antibodies/genetics ; COVID-19 ; Pandemics ; Antibodies, Neutralizing ; Spike Glycoprotein, Coronavirus/genetics ; Protein Binding
Chemical Substances	Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) ; Single-Domain Antibodies ; Antibodies, Neutralizing ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2
Language	English
Publishing date	2023-06-19
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.28875
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 1320: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Protein structure analysis of the interactions between SARS-CoV-2 spike protein and the human ACE2 receptor: from conformational changes to novel neutralizing antibodies.

Mercurio, Ivan / Tragni, Vincenzo / Busto, Francesco / De Grassi, Anna / Pierri, Ciro Leonardo

Cellular and molecular life sciences : CMLS

2020 Volume 78, Issue 4, Page(s) 1501–1522

Abstract: The recent severe acute respiratory syndrome, known as Coronavirus Disease 2019 (COVID-19) has spread so much rapidly and severely to induce World Health Organization (WHO) to declare a state of emergency over the new coronavirus SARS-CoV-2 pandemic. ... ...

Abstract	The recent severe acute respiratory syndrome, known as Coronavirus Disease 2019 (COVID-19) has spread so much rapidly and severely to induce World Health Organization (WHO) to declare a state of emergency over the new coronavirus SARS-CoV-2 pandemic. While several countries have chosen the almost complete lock-down for slowing down SARS-CoV-2 spread, the scientific community is called to respond to the devastating outbreak by identifying new tools for diagnosis and treatment of the dangerous COVID-19. With this aim, we performed an in silico comparative modeling analysis, which allows gaining new insights into the main conformational changes occurring in the SARS-CoV-2 spike protein, at the level of the receptor-binding domain (RBD), along interactions with human cells angiotensin-converting enzyme 2 (ACE2) receptor, that favor human cell invasion. Furthermore, our analysis provides (1) an ideal pipeline to identify already characterized antibodies that might target SARS-CoV-2 spike RBD, aiming to prevent interactions with the human ACE2, and (2) instructions for building new possible neutralizing antibodies, according to chemical/physical space restraints and complementary determining regions (CDR) mutagenesis of the identified existing antibodies. The proposed antibodies show in silico high affinity for SARS-CoV-2 spike RBD and can be used as reference antibodies also for building new high-affinity antibodies against present and future coronaviruses able to invade human cells through interactions of their spike proteins with the human ACE2. More in general, our analysis provides indications for the set-up of the right biological molecular context for investigating spike RBD-ACE2 interactions for the development of new vaccines, diagnostic kits, and other treatments based on the targeting of SARS-CoV-2 spike protein.
MeSH term(s)	Angiotensin-Converting Enzyme 2/chemistry ; Antibodies, Neutralizing/chemistry ; COVID-19/virology ; Humans ; Models, Molecular ; Protein Binding ; Protein Interaction Domains and Motifs ; Receptors, Coronavirus/chemistry ; SARS-CoV-2/chemistry ; Spike Glycoprotein, Coronavirus/chemistry
Chemical Substances	Antibodies, Neutralizing ; Receptors, Coronavirus ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2 ; 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	Switzerland
Document type	Journal Article
ZDB-ID	1358415-7
ISSN	1420-9071 ; 1420-682X
ISSN (online)	1420-9071
ISSN	1420-682X
DOI	10.1007/s00018-020-03580-1
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 195: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article ; Online: Protein structure analysis of the interactions between SARS-CoV-2 spike protein and the human ACE2 receptor

Mercurio, Ivan / Tragni, Vincenzo / Busto, Francesco / De Grassi, Anna / Pierri, Ciro Leonardo

Cellular and Molecular Life Sciences ; ISSN 1420-682X 1420-9071

from conformational changes to novel neutralizing antibodies

2020

Keywords	Molecular Medicine ; Cell Biology ; Molecular Biology ; Pharmacology ; Cellular and Molecular Neuroscience ; covid19
Language	English
Publisher	Springer Science and Business Media LLC
Publishing country	us
Document type	Article ; Online
DOI	10.1007/s00018-020-03580-1
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Protein structure analysis of the interactions between SARS-CoV-2 spike protein and the human ACE2 receptor: from conformational changes to novel neutralizing antibodies.

Mercurio, Ivan / Tragni, Vincenzo / Busto, Francesco / De Grassi, Anna / Pierri, Ciro Leonardo

bioRxiv

Abstract: The recent severe acute respiratory syndrome, known as Corona Virus Disease 2019 (COVID-19) has spread so much rapidly and severely to induce World Health Organization (WHO) to declare state of emergency over the new coronavirus SARS-CoV-2 pandemic. ... ...

Abstract	The recent severe acute respiratory syndrome, known as Corona Virus Disease 2019 (COVID-19) has spread so much rapidly and severely to induce World Health Organization (WHO) to declare state of emergency over the new coronavirus SARS-CoV-2 pandemic. While several countries have chosen the almost complete lock-down for slowing down SARS-CoV-2 spread, scientific community is called to respond to the devastating outbreak by identifying new tools for diagnosis and treatment of the dangerous COVID-19. With this aim we performed an in silico comparative modeling analysis, which allows to gain new insights about the main conformational changes occurring in the SARS-CoV-2 spike protein, at the level of the receptor binding domain (RBD), along interactions with human cells angiotensin converting enzyme 2 (ACE2) receptor, that favour human cell invasion. Furthermore, our analysis provides i) an ideal pipeline to identify already characterized antibodies that might target SARS-CoV-2 spike RBD, for preventing interactions with the human ACE2, and ii) instructions for building new possible neutralizing antibodies, according to chemical/physical space restraints and complementary determining regions (CDR) mutagenesis of the identified existing antibodies. The proposed antibodies show in silico a high affinity for SARS-CoV-2 spike RBD and can be used as reference antibodies also for building new high affinity antibodies against present and future coronavirus able to invade human cells through interactions of their spike proteins with the human ACE2. More in general, our analysis provides indications for the set-up of the right biological molecular context for investigating spike RBD-ACE2 interactions for the development of new vaccines, diagnosis kits and other treatments based on the usage or the targeting of SARS-CoV-2 spike protein.
Keywords	covid19
Language	English
Publishing date	2020-04-18
Publisher	Cold Spring Harbor Laboratory
Document type	Article ; Online
DOI	10.1101/2020.04.17.046185
Database	COVID19

Full text online

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article: Protein structure analysis of the interactions between SARS-CoV-2 spike protein and the human ACE2 receptor: from conformational changes to novel neutralizing antibodies

Mercurio, Ivan / Tragni, Vincenzo / Busto, Francesco / De Grassi, Anna / Pierri, Ciro Leonardo

Cell. mol. life sci

Abstract	The recent severe acute respiratory syndrome, known as Coronavirus Disease 2019 (COVID-19) has spread so much rapidly and severely to induce World Health Organization (WHO) to declare a state of emergency over the new coronavirus SARS-CoV-2 pandemic. While several countries have chosen the almost complete lock-down for slowing down SARS-CoV-2 spread, the scientific community is called to respond to the devastating outbreak by identifying new tools for diagnosis and treatment of the dangerous COVID-19. With this aim, we performed an in silico comparative modeling analysis, which allows gaining new insights into the main conformational changes occurring in the SARS-CoV-2 spike protein, at the level of the receptor-binding domain (RBD), along interactions with human cells angiotensin-converting enzyme 2 (ACE2) receptor, that favor human cell invasion. Furthermore, our analysis provides (1) an ideal pipeline to identify already characterized antibodies that might target SARS-CoV-2 spike RBD, aiming to prevent interactions with the human ACE2, and (2) instructions for building new possible neutralizing antibodies, according to chemical/physical space restraints and complementary determining regions (CDR) mutagenesis of the identified existing antibodies. The proposed antibodies show in silico high affinity for SARS-CoV-2 spike RBD and can be used as reference antibodies also for building new high-affinity antibodies against present and future coronaviruses able to invade human cells through interactions of their spike proteins with the human ACE2. More in general, our analysis provides indications for the set-up of the right biological molecular context for investigating spike RBD-ACE2 interactions for the development of new vaccines, diagnostic kits, and other treatments based on the targeting of SARS-CoV-2 spike protein.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #631796
Database	COVID19

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Details ▾

Article ; Online: Protein structure analysis of the interactions between SARS-CoV-2 spike protein and the human ACE2 receptor: from conformational changes to novel neutralizing antibodies

Mercurio, Ivan / Tragni, Vincenzo / Busco, Francesco / De Grassi, Anna / Pierri, Ciro Leonardo

bioRxiv

Abstract	The recent severe acute respiratory syndrome, known as Corona Virus Disease 2019 (COVID-19) has spread so much rapidly and severely to induce World Health Organization (WHO) to declare state of emergency over the new coronavirus SARS-CoV-2 pandemic. While several countries have chosen the almost complete lock-down for slowing down SARS-CoV-2 spread, scientific community is called to respond to the devastating outbreak by identifying new tools for diagnosis and treatment of the dangerous COVID-19. With this aim we performed an in silico comparative modeling analysis, which allows to gain new insights about the main conformational changes occurring in the SARS-CoV-2 spike protein, at the level of the receptor binding domain (RBD), along interactions with human cells angiotensin converting enzyme 2 (ACE2) receptor, that favour human cell invasion. Furthermore, our analysis provides i) an ideal pipeline to identify already characterized antibodies that might target SARS-CoV-2 spike RBD, for preventing interactions with the human ACE2, and ii) instructions for building new possible neutralizing antibodies, according to chemical/physical space restraints and complementary determining regions (CDR) mutagenesis of the identified existing antibodies. The proposed antibodies show in silico a high affinity for SARS-CoV-2 spike RBD and can be used as reference antibodies also for building new high affinity antibodies against present and future coronavirus able to invade human cells through interactions of their spike proteins with the human ACE2. More in general, our analysis provides indications for the set-up of the right biological molecular context for investigating spike RBD-ACE2 interactions for the development of new vaccines, diagnosis kits and other treatments based on the usage or the targeting of SARS-CoV-2 spike protein.
Keywords	covid19
Publisher	BioRxiv; WHO
Document type	Article ; Online
DOI	10.1101/2020.04.17.046185
Database	COVID19

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Details ▾

To top

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

Inter-library loan at ZB MED

Full text online

Kategorien

Inter-library loan at ZB MED

Kategorien

Inter-library loan at ZB MED

Kategorien

Inter-library loan at ZB MED