Both enterovirus (EV) and respiratory syncytial virus (RSV) are respiratory viruses that cause millions of infections each year. Small children, the elderly, immunosuppressed patients and people with certain comorbidities are at risk of serious infections.


EV belongs to the picornaviridae family, a large group of single-stranded RNA-viruses that infects both people and animals. Human EV is divided into EV A-D and rhinovirus (RV) A-C.

More than 250 different human pathogenic EVs have been identified and new viruses are identified on an ongoing basis. EVs have been estimated to cause more than one billion human infections each year. As with many other RNA viruses, including coronaviruses, EVs mutate frequently and may be transmitted between human and animals, increasing the risk of serious infections and pandemic transmission.

“EV has been estimated to cause more than one billion human infections each year.”

EV primarily replicates in the gut and respiratory system, but the virus may spread to other organs and cause disease. A majority of EV infections are either asymptomatic or cause only mild disease (e.g., the common cold). But EVs may also cause serious diseases (e.g., meningitis, encephalitis, sepsis, myocarditis and paralytic disease) and death in vulnerable individuals.

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Respiratory Syncytial virus (RSV)

Each year, it has been estimated that, RSV causes about 30 million acute lower respiratory tract infections, about 3.2 million hospital admissions and more than 100,000 deaths. From a global perspective, RSV is a major cause of pediatric hospitalizations and deaths. In adults, RSV accounts for about 5–15% of the pneumonia cases during RSV season and, in the US, 11,000–17,000 adults die each year while tenfold more are admitted to the hospital with respiratory complications. In the US, the annual cost of RSV is estimated to be more than $600 million. It is worth noting that RSV hospitalizations are 16 times more prevalent than influenza hospitalizations.

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CUR-N399 is an HTA that targets the PI4KB enzyme with high affinity. This enzyme is located in the Golgi apparatus and is used by all EVs during replication. By inhibiting PI4KB, the EV is prevented from multiplying.

CUR-N399 is the candidate drug selected for clinical development following the design, synthesis and screening of hundreds of PI4KB inhibitors. CUR-N399 displays potent antiviral effects in the micro to lower nanomolar range for all EVs tested. Tested EVs include virus representatives from the EV subgroups EV-A, EV-B, EV-C and EV-D, and rhinoviruses RV groups RV-A and RV-B. Studies have shown a potent antiviral effect and reductions in virus-induced inflammation in several infection models.

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Phosphatidylinositol 4-kinase III beta (PI4KB)

Phosphatidylinositol 4-kinases (PI4Ks) are involved in the replication of several viruses, including EVs. P14Ks have been identified as potential antiviral targets.

PI4Ks synthesize phosphatidylinositol 4-phosphate, are evolutionarily conserved, and include several human isoforms. They regulate trafficking between the Golgi and the membrane. It has been shown that several RNA viruses, including EV, may hijack PI4Ks and use the PI4K-enriched organelle membranes as replication platforms.

PI4KB, one of the PI4K protein isoforms, has been shown to be important in the replication of EVs specifically, and high levels of this protein are present in EV replication membranes throughout infection. PI4KB was selected as a target for Curovir’s novel EV antivirals based on the anticipation that inhibiting PI4KB would counteract EV infection by preventing the virus from replicating.

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Pleconaril is a direct acting antiviral (DAA) that is mainly effective on the rhinovirus subgroup of EV. The drug was developed in the 1990s for treating the common cold and exacerbations of asthma.

Pleconaril exerts its effects by acting directly on the virus, interfering with several processes in the virus’s replication. In 2001, Viropharma, Inc. submitted a new drug application to the FDA for use of pleconaril in the treatment of the common cold. The application was rejected based on safety concerns mainly attributable to the risk of serious drug interaction due to its effects on the CYP3A4. Pleconaril has also been used in several compassionate use programs for the treatment of serious EV infections.

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