Bando a Cascata 2024 del Research Node 5 - Nuovi Antivirali contro i meccanismi di ingresso e replicazione cellulare di Influenza A

Influenza is a widespread acute respiratory disease and represents a serious public health problem, so much so that it weighs on the company both in terms of direct costs (treatments, hospitalizations in the most severe cases) and indirect costs (lost working days, loss of productivity associated with it), and for complications in fragile subjects. The flu has viral origin and spreads easily between people by air, circulates throughout the world and can affect any individual of any age.

The main characteristics of the virus is its high mutagenic capacity, through the antigenic variability in the two glycoproteins HA and NA: it is precisely through this mechanism that the virus evades the immune response of the host organism.

When a completely new strain of influenza appears, capable of transmitting rapidly from human to human on a large scale, a pandemic can occur. Influenza type A has been responsible for 4 major pandemics in the last 100 years and is considered one of the viruses at greatest risk of spillover from animal reservoirs. WHO data indicates that annual epidemics worldwide cause around one billion cases of influenza, three to five million cases of serious illness and 290'000 to 650'000 deaths.

The European Center for Disease Control (ECDC) estimates that every year in Europe, 4 to 50 million symptomatic cases of influenza occur and that 15'000/70'000 European citizens die each year from causes associated with influenza.

The clinical burden of influenza goes beyond common respiratory complications: there is an association between influenza syndrome and cardiovascular events such as heart attack, heart failure and stroke. The only antivirals recommended for the treatment and prevention of human influenza caused by AH1N1 viruses are oseltamivir (marketed under the name Tamiflu®) and zanamivir (Relenza®). Other antiviral drugs that have been in use for a much longer time such as amantadine and rimantadine are no longer effective as influenza viruses have developed resistance to them.

Projects responding to this call should aim to identify new chemical entities capable of counteracting entry by endocytosis mediated by the interaction between the HA protein of the virus and the sialic acid cellular receptor and/or the replication and multiplication of the virus in the infected cell.

Expected Results:

• at least one new class validated on cellular models of antivirals against the influenza A virus to be started in preclinical and/or clinical studies.

• Calls will be open to teams including both private and public entities located in Sourthern Italy (fixed number of 2 entities), external to the INF-ACT consortium and to members of the beneficiary team of the COC-1-2023-CNR call.
• Each team must identify a lead organization (Leader), or the subject appointed and authorized to represent the whole team and maintain communications with the Spoke during all phases of the presentation and evaluation procedure and for the entire duration of the activities planning;
• The team Leader must be a public University or a public Research Organization;
• Each team Leader may submit only one project proposal in response to this call. On the other hand, the possibility is not precluded for the same entity to be part of other teams in response to other Cascade Calls
• Each team entity must indicate the name of the researchers involved in the proposed project activities (so-called "critical mass"), the expected commitment in person-months, their curriculum vitae to assess the actual contribution to the research work.
• Each team entity must participate with at least one researcher. The maximum number of researchers to be involved as critical mass for this project is 4.
• 100% of the requested financing must be dedicated to entities located in regions of Southern Italy (tagging: territorial);
• In case of recruitment of new researchers, the team must comply with the provisions of article 47 "Equal opportunities, generational and gender, in public contracts PNRR and PNC" of Law Decree 31-May-2021, no. 77 converted into law 29-July-2021, n. 108;
• Budget breakdown and financial reporting must comply with guidelines and regulation for RRNP funded-projects.

The call text (in Italian) was published on the CNR website.

Collection of applications started at 12:00 PM on May 7, 2024 and closed at 12:00 PM on June 10, 2024
Evaluations are currently in progress

• All allocated funds must be spent by the end of October 2025. Should MUR allow time extensions to the NRRP/PNRR INF-ACT project, extensions might be also provided to COC projects;
• Awarded teams will comply to NRRP/PNRR reporting rules as per the indications that will be made by INF-ACT Spoke and INF-ACT Foundation;
• Awarded teams will have to join the INF-ACT foundation as partners;
• Funding should be acknowledged in all publications emanating from the research carried out during the award period together with NRRP/PNRR funds using the following statements: "This research was supported by EU funding within the NextGenerationEU-MUR PNRR Extended Partnership initiative on Emerging Infectious Diseases (Project no. PE00000007, INF-ACT). [BENEFICIARY NAME] was recipient of INF-ACT Cascade Open Call 2024 (ID CALL)."
• Participation of private entity and co-financing are not mandatory, but an added value;
• Financial capacity of private entity will be assessed ex-post by third parties. In case of negative outcome, the private entity will be excluded from participating to the awarded project and, therefore, from receiving funding.

Proposals are being evaluated on the basis of the following evaluation criteria:

• Objective and scientific quality (max 50 points)
• Innovation and private sector involvement (max 20 points)
• Impact (max 15 points)
• Economic sustainability (max 15 points)

Proposals will be considered admissible for financing if they obtain at least 70 out of 100 points. Evaluation will be carried out by a panel of 3-5 international and highly-qualified scientists, who are not directly involved in the INF-ACT Research Program. Reviewers will sign a declaration to exclude possible conflicts of interest before accessing the scientific proposals to be evaluated.