## 1 Introduction  
### Pre-Proposal Context  
Enteroviruses (EV) are a highly diverse genus of small, icosahedral viruses with single-stranded, positive-sense RNA genomes [1]. They cause a wide range of human diseases occurring most frequently in infants and young children, such as non-specific febrile illness, exanthemas, respiratory tract infections, and ocular infections. Although infections caused by non-polio enteroviruses (NPEV) are usually benign, they can be severe and have deleterious outcomes in some patients, particularly in children and immunocompromised patients. The enterovirus genus presents seven human pathogen species (EV-A, EV-B, EV-C, EV-D and RV-A, RV-B, RV-C) divided into 11 subgroups: polioviruses (PV), cossackeiviruses groups (CVA, CVB), echowiviruses (E), four enterovirus subgroups, named from A to D, and rhinovirus (RV) classified into RV-A, RV-B and RV-C subgroups. Whole enterovirus RNA strands are always composed of a coding region divided into three parts which are translated into polyproteins that are co-translationally and post-translationally cleaved by viral proteases to produce structural and non-structural proteins [2]. Viruses of the Enterovirus genus share several conserved protein motifs in the RNA-dependent RNA polymerase, capsid proteins, viral proteases, and other non-structural proteins. The emergence of new viral types, such as enterovirus-A71 (EV-A71) and enterovirus-D68 (EV-D68), have been associated with more severe disease manifestations than previously described, including sepsis, myopericarditis, and central nervous system infections [3; 4; 5]. The worldwide prevalence and species distribution of enteroviruses varies among continents. For example, Enterovirus D68 is most prevalent in North America, while Enterovirus B is the predominant variant in Africa, Europe, and Southern Asia. However, there is a more variable distribution of variants among other continents, where a mixture of Enterovirus A71, Coxsackievirus A, and Enterovirus B are the most represented [6]. NPEVs can cause a wide range of health disorders with varying presentation and severity, most often in pediatric and immunocompromised patients. NPEV neonatal diseases are often related to nonspecific symptoms but can lead to severe or fatal clinical situations [7]. When considering epidemiological data, the most common pathogens with the highest incidence are due to EV-A, principally with hand, foot, and mouth disease (HFMD), whose etiologic agents are EV-A71, CVA6, CVA10, and CVA16. EV-A infections have been linked with other diseases. For example, EV-A71 or Echovirus E11 may be the causative agents of severe and life-threatening neurological symptoms--often involving long-term sequelae and cardiopulmonary complications [8]. Recently, EV-A71 has been reported to cause serious epidemics in Asia that are related to severe neurological complications like poliomyelitis [9]. Moreover, acute hemorrhagic conjunctivitis (AHC) was signaled during EV-A70 or CVA24 infections [10]. The second most represented enterovirus is EV-B, which includes Echoviruses E30, E6, E11, and Cossackievirus B3 [6]. Severe EV-B infections have been linked mainly to acute flaccid paralysis (AFP). Meningitis or encephalitis can also be linked to EV-B infections, especially with Echovirus 30. Likewise, myocarditis is mainly induced by the CVB subgroup (from CVB1 to CVB6), and Echovirus 11 [11]. CVB1 can also cause severe infections in infants that may lead to sepsis [12]. Moreover, in 2023, at least 7 European countries experienced an outbreak of Echovirus 11, leading to serious conditions in newborns [12]. Eventually, EV-D species cause mainly pneumonia, bronchiolitis, or acute flaccid myelitis (AFM) [3]. For instance, EV-D comprises the re-emergent EV-D68, recently responsible for epidemics of respiratory diseases and polio-like paralysis AFM leading to death in some cases [13]. Interestingly, European countries have observed a re-emergence of EV-D68 post-COVID-19 lockdown [14].