[Ziresovir: a potent, selective, and oral inhibitor of the respiratory syncytial virus fusion (F) protein]

[齐雷索韦:一种强效、选择性的口服呼吸道合胞病毒融合(F)蛋白抑制剂]

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Abstract

In 2023, a monoclonal antibody (niservimab) specifically targeting the "zero site (Φ)" of the prefusion form of the RSV F protein was marketed in Spain. Various studies have demonstrated its high efficacy in preventing hospitalization and ICU admission in patients with RSV. However, the high cost of this monoclonal antibody, unaffordable in many developing countries, its inaccessibility, or religious beliefs may prevent its routine use in infants worldwide. Therefore, new treatment prospects have been explored through the development of low-cost, orally administered antiviral drugs that can be used anywhere, with or without the monoclonal antibody. In 2014, Ark Biosciences registered Roche's compound RO-0529 for clinical development and named it AK0529; in 2019, it was definitively designated ziresovir. This compound emerged from a program searching for RSV F protein inhibitors based on the benzoazepinequinoline compound. The data available to date suggest that ziresovir is a potent antiviral inhibitor of RSV F protein. When administered orally twice daily for 5 days, it produces a clear clinical improvement in bronchiolitis (signs and symptoms) and a decrease in viral load in the respiratory tract. This new antiviral is well tolerated with few adverse effects, but with the development of resistance during treatment in 11-18% of cases, especially at high doses.

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