1. Development of an animal model and accelerated development of a DNA vaccine candidate
(SCARD SARS-CoV-2 project)
Aims:
- To develop a mouse model of SARS-CoV-2 infection.
This will not only enable us to evaluate the efficacy of the vaccine; it will also facilitate in vivo research on SARS-CoV-2.
- To evaluate the immunogenicity (ability to induce a specific immune reaction) and efficacy (protection capability) of DNA-based vaccine candidates.
DNA vaccination is a technique for protecting against disease by injecting DNA encoding a specific antigen. The injected DNA triggers a protective immunological response, for example the production of antibodies against the antigen. DNA vaccines offer potential advantages compared with conventional vaccines, including the ability to induce a wider range of immune response types. Two antigen candidates have already been designed, based on the S (spike) protein of the virus, responsible for the "crown" ("corona" in Latin) observed at the surface of coronaviruses, after which they were named.
KNOWLEDGE OF THE VIRUS AND ITS PATHOGENESIS
2. Evolution of SARS-CoV-2 and the antibody immune response in humans during infection
(SARS-CoV-2_EVOLSERO project)
Aim: to understand the evolution of the SARS-CoV-2 viral population in hosts during illness, in relation with the infectivity of the virus and the establishment of the humoral (antibody-based) immune response. This knowledge is important to identify trends in disease progression and help improve the treatment and post-treatment follow-up given to patients. Detailed data on the evolution of the SARS-CoV-2 population in relation with disease progression, antiviral treatment and viral shedding sites will also be useful in evaluating links with disease severity and the potential failure of antiviral treatments.
The aim is to elucidate the kinetics of SARS-CoV-2 shedding in patients with Covid-19, depending on the severity of the disease, age and existing comorbidities (shedding in upper respiratory tracts – from the nose to the larynx – and lower respiratory tracts – from the windpipe to the alveoli, or at non-respiratory sites), and also to analyze the kinetics of the viral load at respiratory and non-respiratory sites in confirmed cases according to severity, age group and existing comorbidities. The project also intends to determine the correlation between the development of the viral load and infectivity, and to understand the kinetics of introducing a neutralizing humoral response (the body's production of antibodies to neutralize the virus).
DEVELOPMENT OF RESEARCH TOOLS
3. Development of cell lines for research
(FlipSARS project)
Aim: to generate a line of specific cells that will serve as a basis to improve characterization of the SARS-CoV-2 coronavirus. The generated cell lines will be useful in facilitating the isolation of clinical samples of coronavirus and in carrying out high-throughput screening
KNOWLEDGE OF THE VIRUS AND ITS PATHOGENESIS
4. A technique to identify key cellular factors for SARS-CoV-2 infection
(CoV-CRISPR project)
Aim: to carry out CRISPR/Cas9 tests to identify cellular factors involved in infection with SARS-CoV-2 and antiviral proteins that inhibit its replication. These approaches will lead to the identification of key cellular factors that may serve as virulence determinants and therapeutic targets.
This research particularly concerns lung cells, the main targets of the virus.
EPIDEMIOLOGICAL RESEARCH
5. Building a collection of human biological samples in France
(CORSER project – A seroepidemiological study of the SARS-CoV-2 virus)
Aim: to detect the presence of specific SARS-CoV-2 antibodies in different populations, either those who traveled to China in the weeks preceding the start of the outbreak, or those with suspected infection with SARS-CoV-2. The aim is to understand:
- When and how the virus was transmitted from animals to humans
- When the virus began circulating in humans in France
- How long the infectious period lasts
- What percentage of patients experience few or no symptoms
To answer these questions, the scientists will carry out the first seroepidemiological studies (detecting coronavirus antibodies in patients) of SARS-CoV-2 infection, while also developing a serological test. Samples will be taken:
- from subjects who traveled to China during the period from August 1, 2019 to January 31, 2020 and who were not diagnosed as infected with SARS-CoV-2 (CORSER-1);
- from suspected cases of SARS-CoV-2 infection that tested negative for the virus with the RT-PCR assay on a respiratory sample; contacts or individuals exposed to confirmed cases of SARS-CoV-2 infection; or individuals who worked or stayed in a hospital where confirmed cases of SARS-CoV-2 infection were treated (CORSER-2).
DEVELOPMENT OF RESEARCH TOOLS
6. Antibody profiling in recovering patients and development of a serological test for an epidemiological survey in individuals exposed to SARS-CoV-2
(SARS-CoV-2-LIPS project)
Aim: to develop a test that can be used to carry out an initial survey on the prevalence of antibodies in individuals exposed to the SARS-CoV-2 coronavirus. The aim is to obtain a specific serological test that can be used for high-throughput testing for Covid-19 infection.
KNOWLEDGE OF THE VIRUS AND ITS PATHOGENESIS
7. SARS-CoV-2 fusion, replication and host responses
(CoronaFusion project)
Aim: to use cell cultures and mouse models to analyze the role of interferons and IFITMs (interferon-induced transmembrane proteins) in the replication and pathology of the SARS-CoV-2 virus.
THERAPEUTIC RESEARCH
8. Defective viral genomes (DVGs), potential antiviral inhibitors of SARS-CoV-2
(SARS-DVGs project)
Aim: to use a pipeline to identify the best DVG candidates (molecules known to inhibit viral populations). The pipeline has proven effective in several virus families such as the MERS and murine (MHV) coronaviruses. The scientists propose to use the same method for SARS-CoV-2 and to test the five best DVG candidates on cell cultures. This could lead to DVGs being brought to market as an antiviral treatment for SARS-CoV-2.
DVGs are defective viral genomes capable of hijacking the replication machinery of wild-type viruses and partially or totally inhibiting viral populations. Thousands of different DVGs are produced during infection by one of these viruses. The scientists have developed a method to select those most likely to have antiviral potential.
KNOWLEDGE OF THE VIRUS AND ITS PATHOGENESIS
9. Profiling SARS-CoV-2 intra-viral and virus-host interactions on the basis of innate immunity signaling
(PSII project)
Aim: the coronavirus replication cycle depends on several protein-protein interactions, some between viral proteins to generate functional protein complexes and others with host proteins to inhibit the innate immune response. Identifying these interactions, which are essential for viral infection, can reveal the molecular mechanisms involved in pathogenesis and identify weak points in the virus that may be potential therapeutic targets.
KNOWLEDGE OF THE VIRUS AND ITS PATHOGENESIS
10. Working towards controlled detection of SARS-CoV-2 by the innate immune system
(CoV-2Sensing project)
Aim: controlling the SARS-CoV-2 outbreak requires both scientific knowledge and antiviral drugs. RIG-I-like receptors in the cell cytoplasm play a major role in detecting infection with RNA viruses and in initiating and modulating antiviral immunity. The aim of the project is to study the RNA ligands in the SARS-CoV-2 virus that are detected by these receptors. The project will shed light on the innate immune response to SARS-CoV-2, including the harmful effects of the immune response, thereby helping identify strategies for the design of broad-spectrum antiviral drugs and vaccine adjuvants.
DEVELOPMENT OF RESEARCH TOOLS
11. A SARS-CoV-2 genome sequencing technique to analyze low-quality clinical samples
(SABSOS project)
Aim: viral genomics is a key tool in the response to emerging disease outbreaks like that caused by SARS-CoV-2. But sequencing can be difficult because of poor quality samples or the low ratio of viral to host RNA. This technical project will implement and optimize an approach for processing clinical samples even if they are of poor quality and have a low viral load.
This method has worked for other RNA viruses (chikungunya using samples with a very low load; dengue virus using individual mosquitoes; degraded Zika virus samples).
KNOWLEDGE OF THE VIRUS AND ITS PATHOGENESIS
12. Origins, natural reservoirs and interspecies transmission of SARS-CoV-2 and other SARS-like coronaviruses
(ONRITS project)
Aim: to improve understanding of the origins, natural history and dissemination of SARS-CoV-2 and SARS-like coronaviruses in their natural environment. The main focus is to shed light on interspecies transmission (among bats, between bats and other animals, and between bats and humans); this is vital to mitigate the effects of future outbreaks like the devastating pandemic we are currently witnessing with SARS-CoV-2.
It is crucial to determine which bat species serve(s) as natural reservoirs for SARS-CoV-2. This project will involve collecting biological samples (oral and fecal swabs, blood and urine samples) from bats and testing them for SARS-CoV-2 or other SARS-CoVs to determine their natural host.
Bat fly ectoparasites and flying hematophagous insects (sand flies, mosquitoes and biting midges) will also be tested for the virus, since they may play a role in transmitting SARS-CoVs from one bat to another. Interactions with other animals will be observed to identify other potential hosts (snakes, civet cats or pangolins).
DEVELOPMENT OF RESEARCH TOOLS
13. Development of simple Covid-19 serological tools and targeted serosurvey of at-risk individuals
(COVID-19 Serosurvey project)
Aim: to develop simple serological tools that can be used to establish three tests: an enzyme-linked immunosorbent assay (ELISA), an immunofluorescence assay (IFA) and multiplex microsphere-based immunoassays (MIAs – capable of detecting several targets). This research will pave the way for the serological investigation of at-risk individuals such as those working at animal markets, farmers exposed to bat guano (used as a natural fertilizer) and those living in rural villages in Cambodia. Biological samples are available at the Institut Pasteur du Cambodge because of previous and current research conducted by the Virology Unit.
SARS-CoV-2 diagnosis has hitherto been based on molecular biology methods (RT-PCR). Serological surveys, especially in at-risk individuals, will be a vital tool in improving our understanding of the epidemiology of the novel virus.
VACCINE CANDIDATES
14. Spike glycoprotein, lentiviral vectors and B/T-cell vaccine
(VAC-NAB-COV project, by Pasteur/TheraVectys Joint-Lab)
Aims: to develop as quickly as possible:
- an in vitro test to detect and quantify SARS-CoV-2 neutralizing antibodies while avoiding the need to handle the virus. The test will be used to demonstrate the feasibility of vaccine candidates (proof of concept).
The availability of a test of this type is crucial in searching for antibodies in samples from patients with Covid-19. These tools will be produced in large quantities and made available to all Institut Pasteur teams.
- a prophylactic vaccine candidate for SARS-CoV-2 based on lentiviral vaccine vectors.
These lentiviral vaccine vectors encode immunogens that protect against SARS-CoV-2 viral surface proteins (spike or nucleocapsid). They will be investigated in an animal model.
Lentiviral vaccine vectors are particularly useful because of their potential to induce long-lasting adaptive immune responses. Scientists have already demonstrated the remarkable protective efficacy of these vectors in mice in several situations (against infection with papillomavirus and some flaviviruses, for example) and a lentiviral vector (LV) has also been successfully investigated in a phase 1 trial for an HIV vaccine, which established its safety in humans.
DEVELOPMENT OF DIAGNOSTIC TESTS
15 . Production of recombinant antigens from two SARS-CoV-2 proteins and generation of nano-antibodies against these proteins for diagnostic and therapeutic applications
(CORONABODIES project)
Aim: to develop reliable rapid diagnostic tests for the infection that can be performed in a few minutes, anywhere and at any time, outside research laboratories; and serological tests to monitor the spread of the outbreak virtually in real time, helping with the implementation of mitigation measures.
The idea is to generate the following unique tools as quickly as possible:
recombinant SARS-CoV-2 nucleoprotein (N) and spike (S) antigens;
nano-antibodies targeting these two proteins.
These tools will be used to develop:
- serological tests for a serological survey of the exposed population, to help sort suspected cases and enable real-time monitoring of the spread of the outbreak;
- antigen detection tests that can be used for quick and effective sorting of suspected cases.
Neutralization of the virus with "anti-S" nanobodies will also provide direct options for clinical therapeutic development.
KNOWLEDGE OF THE VIRUS AND ITS PATHOGENESIS
16. Monitoring the origins and transmission/spread of SARS-CoV-2 in Laos and Vietnam: searching for SARS-like viruses and detecting antibodies in vertebrates
(SPILLOVER-CORONA project)
Collaborative project between the Institut Pasteur in Paris, the Institut Pasteur du Laos and the National Institute of Hygiene and Epidemiology in Vietnam.
Aims:
- to search for other SARS-like coronaviruses in various vertebrates and arthropods.
A metagenomic analysis will be carried out using next-generation sequencing (NGS) technologies on selected samples.
- to detect past coronavirus infections in animals and humans exposed to the virus.
This research will use antibody tests specifically developed within the Institut Pasteur's coronavirus task force for SARS-CoV-2, adapting them to the newly identified coronaviruses.
The project complements (and it is conducted in conjunction with) a project at the Institut Pasteur du Laos: "Origins, natural reservoirs and interspecies transmission of SARS-CoV-2 and other SARS-like coronaviruses" (ONRITS) (see project 12), which aims to improve understanding of the origins, natural history and dissemination of SARS-CoV-2 and other SARS-like CoVs in their natural environment, as well as potential bat-to-bat, bat-to-animal and bat-to-human transmission mechanisms.
THERAPEUTIC RESEARCH
17. Isolating and characterizing the human antibodies that neutralize SARS-CoV-2
(2019-NCOV THERAMAB project)
Aim:
to elucidate the mechanisms behind the antibody responses to SARS-CoV-2 and investigate the role they may play in eliminating the virus in infected individuals. The idea is to improve our understanding of the antibody responses of anti-SARS-CoV-2 memory B lymphocytes at molecular and functional level (B lymphocytes are the immune cells that produce antibodies). The memory B cells that develop after an initial infection have a long life span and are capable of intervening rapidly and effectively in the event of reinfection. The project aims to harness the discoveries made to develop a treatment based on the use of human neutralizing antibodies (immunotherapy).
KNOWLEDGE OF THE VIRUS AND ITS PATHOGENESIS
18. Characterization of interaction between SARS-CoV-2 Nsp3 protein and non-canonical nucleic acid structures (G4) present in infected cells
(G4-COVID19 project)
Aim: to characterize the molecular interaction of the SARS-CoV-2 virus, and particularly two domains of its Nsp3 protein, with non-canonical nucleic acid structures present in human cells. These structures known as G4-RNA and their interaction with Nsp3 constitute new therapeutic targets. Tests developed under this project will enable research on molecules to inhibit such host-virus interaction and potentially block virus replication in infected individuals.
KNOWLEDGE OF THE VIRUS AND ITS PATHOGENESIS
19. A combination of cutting-edge proteomic approaches for improving understanding of SARS-CoV-2 infection mechanisms
(PROTEO-SARS-CoV-2 project)
Aim: to characterize the cellular mechanisms of SARS-CoV-2 infection. Using several cutting-edge mass spectrometry protein analysis techniques, the team is seeking to understand how the virus interacts with human cells. They are particularly interested in cellular mechanisms that enable the virus to modify proteins in infected cells in order to reproduce. This study conducted in tandem with a comparison with other viruses from the coronavirus family may enable new therapeutic targets to be identified.
EPIDEMIOLOGICAL RESEARCH, SOCIAL EPIDEMIOLOGY
20. Red Cross health workers and volunteers and continuity of care with COVID-19: an operational approach using mixed methods
(RCCOVID project)
Aim: to study social and cultural challenges encountered by French Red Cross health workers and volunteers (who work with healthcare facilities/hospitals, nursing homes, etc. as well as those working in the field to assist migrants, homeless people, and frail and elderly people) and monitor communication in mainstream and social media to adapt the response to the pandemic in each region. By combining an ethnographic and big data approach, this project seeks to help mobilize and motivate physicians, nurses, nursing assistants, and volunteers. This work will enable the supply of appropriate equipment, measures and communication tools for their work.
DEVELOPMENT OF RESEARCH TOOLS
21. Generation of animal models sensitive to SARS-CoV-2 to test vaccines or drugs
(hACE2-COV project, by Pasteur/TheraVectys Joint-Lab)
Aim – Rapid development of animal models is of utmost importance to test the efficacy of vaccines and drug against COVID-19. The aim of this research project is to propose models whose cells express the human ACE2 proteins (huACE2) so that they are sensitive to SARS-CoV-2. The ACE2 protein is the gateway for the virus to enter cells. Researchers are proposing to use adenoviruses and lentiviruses as a vector to introduce the huACE2 gene.
PROPHYLAXIS AND CANDIDATE VACCINES
22. Randomized trial of Covid-19 chemoprophylaxis in healthcare professionals
(COVIDAXIS trial)
Objective: To determine whether a two months treatment with hydroxychloroquine (HCQ) or Lopinavir / ritonavir (LPV / r) reduces the incidence of symptomatic or asymptomatic infections with SARS-CoV-2, compared to their placebo, in healthcare professionals exposed to the virus.
In the absence of specific antiviral treatment, particular attention must be paid to prevention. Individual protective equipment can be insufficiently protective, including for healthcare professionals. If this trial confirms the efficacy of either drug, a chemoprophylaxis strategy could be extended to other populations highly exposed to SARS-CoV-2 or at risk of severe forms of Covid-19 while waiting for other preventive tools, vaccines in particular, to become available.
News on May 27, 2020
In accordance with the decision of the French Agency for the Safety of Health Products (Agence Nationale de Sécurité du Médicament et des Produits de Santé or ANSM) about the first part of the Covidaxis trial, the inclusions of participants in the study are suspended and the treatments are stopped.
The independent trial follow-up committee did not observe any signal of toxicity in the trial participants as of 05.28.2020.
Learn more about COVIDAXIS (in French)
DEVELOPMENT OF RESEARCH TOOLS
23. Development of a test to identify inhibitors of SARS-CoV-2 proteases
(Cov2-PIs project)
SARS-CoV-2 proteases are essential to the life cycle of the virus and are highly conserved in the beta-coronavirus family. This is how the Cov2-Pls-project researchers will develop a high-throughput screening system to identify inhibitors that can effectively block the action of SARS-CoV-2 proteases, and thus stop the proliferation of the virus. The molecules identified could help develop, ultimately, effective drugs to control the spread of SARS-CoV-2 and limit its impact on public health and the global economy.
THERAPEUTIC RESEARCH
24. Find potent antiviral drugs against SARS-CoV2 by targeting well identified proteins essential to the viral cycle.
(DrugDesign_SARS2 project)
Aim: The DrugDesign_SARS2 project aims to find effective antiviral drugs against SARS-CoV-2 that target proteins essential to the viral cycle. The project brings together the expertise of several laboratories and platforms of the Institut Pasteur International Network (Paris, Lille, Rome). The aim of the study is to examine a large number of compounds as quickly as possible using high throughput screening techniques. In a second round, the objective will be to improve the selected compounds, by chemical processes and using the data obtained by the various laboratories.
EPIDEMIOLOGICAL RESEARCH, SOCIAL EPIDEMIOLOGY
25. INTERNATIONAL | São Paolo | Descriptive study: epidemiological, clinical and immunological analysis of SARS-CoV-2 cases in the Metropolitan Region of São Paulo, Brazil
(MRSP study)
Aim: to identify and analyze the profile of people infected with the SARS-CoV-2 virus in São Paulo, Brazil. This project will be conducted in the Metropolitan Region of São Paulo, one of the most densely populated areas in the world, where the contact rate is accordingly high. By studying epidemiological, clinical and serological aspects of infected individuals, this work will supplement current limited data on virus behavior and outbreak spread. Examining the individual profiles of pediatric and adult patients is essential for understanding infection with this new virus and COVID-19 as a disease.
DEVELOPMENT OF DIAGNOSTIC TOOLS
26. INTERNATIONAL | São Paolo | Developing a low-cost lab-on-a-chip for diagnosing SARS-CoV-2
(LAMP project)
Aim: Demand for diagnostic tools for SARS-CoV-2 is extremely high. Current RT-PCR-based assays are ultra-sensitive, but also expensive and therefore inaccessible to the poorest countries. Scientists working on the LAMP project have therefore decided to develop a low-cost lab-on-a-chip that is easy to use in the field for diagnosing SARS-CoV-2. Amplification of RNA, which is necessary for detecting the virus, is achieved through an assay based on LAMP technology, which is capable of overcoming some limitations of RT-PCR assays and can be performed in a water bath. Moreover, the reactions generate colors that are visible in tested vials. These simple, low-cost assays are therefore easy to use for detecting SARS-CoV-2 in samples taken in the field.
DEVELOPMENT OF RESEARCH TOOLS
27. INTERNATIONAL | Paris, Dakar, Cameroon, Ivory Coast | Serological surveillance of SARS-CoV-2 and seasonal coronaviruses
(CoronaSeroSurv project)
Aim: Serology is an important complementary tool to real-time PCR for diagnosing SARS-CoV-2, allowing detection of past and current infections. A multiplex Luminex serological assay will be optimized in Paris and transferred to Dakar, Abidjan and Yaoundé where blood samples will be tested for antibodies to SARS-CoV-2 and seasonal coronaviruses. Mathematical models will classify infected individuals and estimate levels of population immunity.
DEVELOPMENT OF RESEARCH TOOLS
28. The use of Artificial Intelligence Methods to Discriminate Covid-19 from other Community Acquired Pneumopathy using Chest X-Ray and CT images
(AIMDP COVID-19 project)
Diagnostic of SARS-CoV-2 Coronavirus caused-disease (Covid-19) is a bottleneck in the immediate follow-up of patients. We propose automated detection methods based on Artificial Intelligence (AI) Algorithms (Machine Learning and Form Recognition), on chest Computed tomography (CT) or X-Ray images, to discriminate the Covid-19 disease from other Community Acquired Pneumonia (CAP). The methods will be used as complement to the reverse-transcription polymerase chain reaction (RT-PCR) tests.
EPIDEMIOLOGICAL RESEARCH, SOCIAL EPIDEMIOLOGY
29. INTERNATIONAL | French Guiana, New Caledonia, Guadeloupe | Household transmission investigation study for SARS in overseas territories
(EPICOVID-19 Project)
Aim: EPI-COVID-19, a research project in epidemiology to study intra-household transmission around cases of Covid-19 confirmed in French Guiana.
The EPI-COVID study, covering 250 households (150 in French Guiana, 50 in Guadeloupe and 50 in New Caledonia), should make it possible to investigate the secondary infection rate, the speed of spread of the virus, the proportion of asymptomatic cases, the incubation period, the contagiousness period and the immune response associated with SARS-CoV-2. These results will be compared with those of less warm and less humid territories than French Guiana.
EPI-COVID focuses on 250 confirmed cases and their household contacts, expecting a total of 600 subjects. The study provides for clinical, virological and serological monitoring of the participants, using blood and nasopharyngeal samples taken from the families' homes. Since March 23, about 80 people have been included in the study in French Guiana.
EPIDEMIOLOGICAL RESEARCH, SOCIAL EPIDEMIOLOGY
30. Covid-19 risk evaluation among the household contacts of the first cases in Africa
(COVID-19 risk evaluation project)
Aim: Once the first Covid-19 cases will be identified, the spread of the SARS-CoV-2 will be related with the level of the transmission risk. This study aims to obtain an early understanding of key epidemiological characteristics in the family contacts in different African countries of the IPIN to inform decision makers about the potential spread and impact of SARS-CoV-2 infection in the closest contacts. The study will be carried out in household with at least 5 persons and during three weeks once the family index cases detected.
EPIDEMIOLOGICAL RESEARCH, SOCIAL EPIDEMIOLOGY
31. INTERNATIONAL / Dakar / Evaluation of clinical presentation and evolution of SARS -CoV-2 coronavirus infection in Senegal
(SEN-CoV project)
Aim: The overall objective of this study is to understand the main clinical, biological, virologic and immunological characteristics of Covid-19 cases detected in Senegal in order to inform the development and updating of health guidelines for cases management and reduce the potential impact of infection. A retrospective and prospective cohort study of Covid-19 confirmed cases will be performed.
EPIDEMIOLOGICAL RESEARCH, SOCIAL EPIDEMIOLOGY
32. INTERNATIONAL / Niger, Dakar, Cameroun, Madagascar / Protocol for assessment of potential risk factors for 2019-novel coronavirus (2019-nCoV) infection among health care workers in a health care setting.
(Healthcare workers Africa project)
Aim: Worldwide, the health care workers play an essential role in the clinical management of Covid-19 patients, but in Africa they are also at risk of infection given the level of control measures in hospital wards. This study aims to obtain an early understanding of key epidemiological characteristics in the risk of transmission in healthcare workers in different African countries of the IPIN to inform decision makers about the potential impact of SARS-CoV-2 infection in this population essential for the continuity of care. The study will be carried out in hospital wards in charge of the first Covid-19 cases.
DEVELOPMENT OF RESEARCH TOOLS
33. INTERNATIONAL / Canada / Developing a rapid diagnostic test to detect SARS-CoV2 virus in various environment
(POC Project)
Aim: The epidemy of the SARS-CoV-2 virus and its global spread urgently requires efficient means for rapid diagnosis, as well as detection in various environments (aside from clinical laboratories), such as airplanes, schools, potential animal carriers, etc. We have previously devised a colorimetric method to detect specific pathogen sequences using Rolling Circle Amplification (RCA) which could potentially be used for “on site” virus detection.
THERAPEUTIC RESEARCH
34 .INTERNATIONAL | Shanghai, Paris | Identification and isolation of potent human neutralizing antibodies against SARS-CoV-2
(NABCOV project)
Aim: Neutralizing antibodies (nAbs) hold great potential to prevent and treat SARS-CoV-2 infections. We propose to clone and express monoclonal antibodies (mAbs) from the IgG+ B cells of convalescent patients directed against SARS-CoV2 Spike (S) protein. Their neutralizing capacity will be tested by using pseudovirus particles and virus infection assays. Finally, the B-cell epitopes will be characterized for the selected neutralizing antibodies (nAbs) by cryogenic electron microscopy (cryo-EM).
THERAPEUTIC RESEARCH
35. INTERNATIONAL | Paris | Accelerating the identification & design of SARS-CoV2 antiviral drugs in combination with the “DrugDesign_SARS2” project
(inSilico_Drugs_to_Beat_SARS2 project)
Aim: to accelerate the identification & design of SARS-CoV-2 antiviral drugs in combination with the “DrugDesign_SARS2” project. FDA-approved Institut Pasteur Paris platforms, and subsequently, wide libraries of purchasable compounds will be screened in silico to target functions/interactions of RNA_Pol, Spike (virus targets) and ACE2 (host targets) proteins. Prioritization will accelerate testing & discovery of inhibitors. in silico modulation/optimization of validated hits will be pursued.
THERAPEUTIC RESEARCH
36. INTERNATIONAL | INRS Canada | Urgent Discovery of Drug Candidates That Target Coronavirus SARS-CoV-2
(DrugCandidates-SARS-CoV-2 project)
Aim: rapidly provide drug candidates to treat victims of Covid-19. We will do this by applying our cutting-edge technologies and libraries to screen for viable active compounds that kill coronavirus. The strategy will employ phenotype screens (FPDD) that test for coronavirus inhibition using mouse (MHV-59) and human (OC43) virus as models for fast compound screening in cell culture. Direct-acting antivirals will also be sought via target-based screening (FBDD) as inhibitors of essential viral proteins of SARS-CoV-2.
EPIDEMIOLOGICAL RESEARCH, SOCIAL EPIDEMIOLOGY
37. INTERNATIONAL | Montevideo | Engineering an ACE2 derived polypeptide for label-free, real-time detection on a smartphone device and therapeutic intervention
(isCoVDe – in silico Coronaviruses Decoy project)
The current pandemic of CoV urges for therapeutic options and fast, and cheap diagnosis in alternative to the PCR based technology. We propose characterizing a newly designed polypeptide based on ACE2, which could be the base of detection devices adapted to smartphones and harbors the potential for therapeutic intervention. Focusing on ACE2 overcomes viral mutations, extending the applicability to this and other Coronaviruses.
EPIDEMIOLOGICAL RESEARCH, SOCIAL EPIDEMIOLOGY
38. INTERNATIONAL | Cameroon, Paris | Evaluation of SARS-CoV-2 infection spread in various populations groups in Cameroon
(infection spread in Cameroon project)
Aim: The high case fatality ratio of Covid-19 compared to the flu is a global preoccupation. It could be related to non-reporting of mild and asymptomatic infection whose role in transmission is not completely clear if not diagnosed. It is therefore of paramount importance to quickly evaluate the true extent of the infection of SARS-CoV-2. We planned it in different population groups (close contacts of confirmed Covid-19, Health care workers (HCW), Travellers from high risk countries, merchants of bushmeat, and blood donors) in Cameroon.
PROPHYLAXIS AND CANDIDATE VACCINES
39. INTERNATIONAL | Bulgaria |Development of novel nano-based multi-epitope vaccine against coronavirus SARS-CoV-2 - Generation of Humanized NSG transfer mouse model for vaccine testing
(VacciNanoCor project)
Aim: We hypothesize that it may be possible to generate protective anti-SARS-CoV-2 immuneresponse in humanized NSG transfer mouse model. This will be achieved by administering to them of lipid-based nanoparticles carrying peptide molecules, comprising dominant immunogenic B and T cell epitopes from coronavirus SARS-CoV-2. The epitopes will be predicted by EpiDOCK server for evaluation of peptide binding to HLA class II proteins.
PROPHYLAXIS AND CANDIDATE VACCINES
40. INTERNATIONAL | Madagascar | Investigation of the first cases of coronavirus (COVID-19) infections and their contacts in Antananarivo, Madagascar
(Covid-19 & contacts Madagascar project)
Aim: This study aims to understand the epidemiologic, clinical, virologic and immunologic characteristics of first infected cases, their evolution and household transmission. It is intended to follow confirmed infected cases and their household members. It will be conducted with clinicians from three hospital centers of Antananarivo.
KNOWLEDGE OF THE VIRUS AND ITS PATHOGENESIS
41. INTERNATIONAL | Paris, KKU | Characterization of variable systemic and mucosal immunity during SARS-CoV-2 infection and recovery
(COVar_Immune project)
Aim: Our knowledge of the kinetics, intensity and diversity of cellular and humoral immune responses following SARS-CoV-2 infection in humans is limited. Using a novel technical pipeline based on the Milieu Interieur cohort approach, we will characterize systemic as well as local mucosal immunity during and after SARS-CoV-2 infection. We aim to identify immune signatures that can distinguish clinical outcomes (recovery versus virus-induced pathologies).
KNOWLEDGE OF THE VIRUS AND ITS PATHOGENESIS
42. Nicotinic modulation of SARS-CoV-2 infection in the brain (NicoSars Project)
Aim: This project aims at experimentally testing the hypothesis that the nicotinic acetylcholine receptor (nAChR) plays a key role in the pathophysiology of Covid-19 infection and might represent a target for the prevention and control of Covid-19 infection.
KNOWLEDGE OF THE VIRUS AND ITS PATHOGENESIS
43. Mechanisms of intercellular spreading of SARS-CoV-2: assessing the role of TNTs to escape immune surveillance and expand tropism and pathogenicity (COVID-Spreads project)
Aim: We will study the mechanism of spreading of SARS-CoV-2 between permissive (eg; epithelial) and non-permissive (eg; neuronal) cells, and investigate the role of TNTs, as well as the dependence on the ACE2 receptor. Our cryoEM and FIBSEM set up, will provide unique structural information about this process. Overall, this project will allow understanding the mechanism of the viral neurotropism, as well explain its immune evasion capacity.
KNOWLEDGE OF THE VIRUS AND ITS PATHOGENESIS
44. Evaluating the determinants of coronavirus tropism in 3D models of human pulmonary epithelia (TROPICORO project - TROPIsm of COROnaviruses)
Aim: This study will compare the tropism of SARS-CoV-2 and more benign human coronaviruses for primary epithelia of the respiratory tract, to determine whether tropism associates with pathogenicity. The research team will use models based on reconstructed human airway epithelia and take advantage of a lung-on-chip technology that mimics the pulmonary alveolae stretch associated with breathing to develop physiologically relevant models of SARS-CoV-2 infection.
KNOWLEDGE OF THE VIRUS AND ITS PATHOGENESIS
45. Neurological implications of SARS-COV-2 infection – a transversal study (Neurological project)
Aim: The infection of the nasal mucosa and the lungs by CoV-2 may spread to the CNS, including the brainstem, thereby playing a potential key role in the severe respiratory distress observed in COVID-19. Although several clinical observations support this hypothesis, the knowledge in this field is very limited. To fill this gap, we will investigate CoV-2 neuroinvasion in humans, animal models, and cell culture-based experimental models and decipher the molecular mechanisms involved. Results of this project will provide clues on whether targeting potential neurotropism of CoV-2 may be relevant approach for experimental therapeutics in Covid-19.
KNOWLEDGE OF THE VIRUS AND ITS PATHOGENESIS
46. INTERNATIONAL | Paris | Restriction of SARS-CoV-2 replication by coding and non-coding genes (ROSA project)
Aim: Knowledge concerning the interaction of SARS-CoV-2 with human cells is sparse. RNA-sequencing analysis, loss-of-function approaches and mechanistic studies will be used to identify and characterize coding and non-coding genes that restrict viral replication. Taking advantage of some of these naturally occurring viral inhibitors may be an effective strategy in the development of novel drugs to treat the disease.
KNOWLEDGE OF THE VIRUS AND ITS PATHOGENESIS
47. Deciphering the virus interactions with the entry receptors in human cells, and their potential inhibition (DSAC project )
Aim: Researchers will develop and employ a workflow that combines cryogenic light and electron microscopy imaging modalities with computational analysis and data mining to determine high-resolution in-situ structural images of the virus-spike interactions with cell receptors and with the antibodies that abrogate their cell entry. These studies will provide a blueprint for the design of vaccines and therapeutics.
DEVELOPMENT OF RESEARCH TOOLS
48. Sequence the complete genome of Covid-19 directly and at low cost from prepared RNA samples from patients (CAPTURE-COV project)
Aim: to be able to sequence the complete genome of Covid-19 directly and at low cost from prepared RNA samples from patients. We plan to implement a capture sequencing protocol targeting the SARS-CoV-2 genome using three commercial sets of probes in parallel. Results will be compared with a bioinformatics analysis pipeline and shared via publication (Biorxiv preprint followed by classical peer review).
DEVELOPMENT OF RESEARCH TOOLS
49. Air monitoring risk area (ARISE project)
Aim: The ARISE project will produce an air analyser equipped with detection capabilities for the ubiquitous monitoring of SARS-CoV-2 pathogens in airborne droplets or aerosols in confined environments. ARISE deals with the development and validation of an analytical chain for the air monitoring of areas at risk of exposure to individuals contaminated by the SARS-CoV2 virus. Knowledge acquired on the presence of viruses in the air will contribute to adapt measures taken for the prevention and control of infection in healthcare settings.
Learn more on CEA-Leti website
DEVELOPMENT OF RESEARCH TOOLS
50. A zebrafish model to study SARS-CoV-2 neuroinvasion (NeuroCoVid project)
Aim: Invasion of the central nervous system, possibly via the olfactory nerve, is suspected to play a role in respiratory failure of Covid-19 patients. This project aims to test SARS-CoV- 2 neuroinvasiveness in vivo in a zebrafish model. The zebrafish larva allows easy visualization of the entire nervous system in vivo or with whole mount fixed samples. It could provide a cheap, genetically tractable model to analyze viruss dissemination in its host and effect of antiviral drugs.
THERAPEUTIC RESEARCH
51. Drug Repurposing & Design to inhibit the SARS-CoV2 proteases (CoV2-Anti-protease project)
Aim: Identification of antiviral molecules targeting SARS-CoV2 proteases. Structures of the proteases will be used to screen large chemical libraries in complement of the FDA approved drugs. High Througput Screening (HTS) using dual mCherry-Nanoluc reporter cell lines can screen thousands of compounds. Combined with virtual screening this allows coverage of a large chemical space including purchasable compounds libraries. The best hits will be further validated on SARS-CoV-2 growth assays. Validated hits will guide optimization of compounds.
DEVELOPMENT OF RESEARCH TOOLS
52. rBCG vaccine secreting SARS-CoV-2 antigens (rBCG vaccine project)
Aim: Mycobacterium bovis BCG is a live attenuated vaccine that is used since almost 100 years for the vaccination against tuberculosis, with a solid safety record in billions of immunocompetent individuals. The aim of the project is to construct recombinant BCG strains that express viral protein(s) of the SARS-CoV-2 virus in fusion with the 6 kD early secreted antigenic target (ESAT-6), secreted by the type VII secretion systems.
KNOWLEDGE OF THE VIRUS AND ITS PATHOGENESIS
53. Investigating the role of apico-basal proteins during SARS-Cov2 infection (EPIC project)
Aim: Manipulation of the apico-basal Polarity pathways during infection is a strategy routinely used by numerous viruses. This leads to the mislocalization or degradation of the polarity proteins and participate to the disruption of the epithelial integrity.
Nothing is known so far concerning SARS-CoV2 and polarity. In order to better understand SARS-CoV2 physiopathology, this study focuses on the expression pattern of apico-basal polarity proteins during SARS-CoV2 infection.
