There is an urgent need for potent and selective antivirals against SARS-CoV-2. Pfizer developed PF-07321332 (PF-332), a potent inhibitor of the viral main protease (Mpro, 3CLpro) that can be dosed orally and that is in clinical development. We here report that PF-332 exerts equipotent in vitro activity against the four SARS-CoV-2 variants of concerns (VoC) and that it can completely arrest replication of the alpha variant in primary human airway epithelial cells grown at the air-liquid interface. Treatment of Syrian Golden hamsters with PF-332 (250 mg/kg, twice daily) completely protected the animals against intranasal infection with the beta (B.1.351) and delta (B.1.617.2) SARS-CoV-2 variants. Moreover, treatment of SARS-CoV-2 (B.1.617.2) infected animals with PF-332 completely prevented transmission to untreated co-housed sentinels. There is an urgent need for anti-virals targeting SARS-CoV-2. One of the most promising viral targets is the main protease of SARS-CoV-2, which is essential for viral replication and has no human analogue. Here, Abdelnabi et al. show that one of the most promising anti-virals (PF-07321332), currently in clinical trials, protects against SARS-CoV-2 alpha, beta and delta variant infection and provide evidence of reduced transmission.
【저자키워드】 SARS-CoV-2, Antiviral agents, 【초록키워드】 Treatment, Antiviral, B.1.351, variant, SARS-CoV-2 variant, Infection, B.1.617.2, clinical trials, Transmission, 3CLpro, protease, Anti-viral, Replication, MPro, Pfizer, Viral, SARS-CoV-2 variants, animals, viral replication, Primary human airway epithelial cells, Alpha, target, Beta, epithelial cells, PF-07321332, Alpha variant, inhibitor, intranasal, Air-liquid interface, Evidence, in vitro activity, epithelial cell, golden hamsters, evidence of, golden hamster, clinical development, selective, primary human airway, Syrian Golden hamsters, PROTECT, reduced, prevented, dosed, 【제목키워드】 variants of concern, Protease inhibitor, hamster, PROTECT, infection with SARS-CoV-2,