Paxlovid: Mechanism of Action, Synthesis, and In Silico Study.
Mahrokh MarziMohammad Kazem VakilMaryam BahmanyarElham ZarenezhadPublished in: BioMed research international (2022)
In this work, the discovery and description of PF-07321332, a major bioavailable oral SARS-CoV-2 protease inhibitor with in vitro human coronavirus antiviral activity, and excellent selection of off-target and in vivo immune profiles are reported. Various drugs and novel compound candidates for the treatment of the COVID-19 pandemic have been developed. PF-07321332 (or nirmatrelvir) is a new oral antiviral drug developed by Pfizer. In response to the pandemic, Pfizer has developed the COVID vaccine and in 2022 will launch its new major anti-SARS-Cov-2 protease inhibitor (PI). The combination of ritonavir and nirmatrelvir is under study in phase III of the clinical trial with a brand name Paxlovid. Paxlovid is an active 3Cl protease inhibitor. Paxlovid exerts its antiviral efficacy by inhibiting a necessary protease in the viral replication procedure. Proteases of coronavirus cleave several sites in the viral polyprotein where pyrrolidone was replaced by flexible glutamine. Due to the coronavirus pandemic, there is high demand for synthesis and development of this novel drug. Herein, we report the synthetic route and the mechanism of action was recently published on nirmatrelvir. Also, a comparison of the performance of two new oral antiviruses (molnupiravir and nirmatrelvir) for the treatment of COVID-19 is described. This review will be helpful for different disciplines such as biochemistry, organic chemistry, medicinal chemistry, and pharmacology.
Keyphrases
- sars cov
- respiratory syndrome coronavirus
- clinical trial
- phase iii
- open label
- endothelial cells
- small molecule
- emergency department
- phase ii
- double blind
- minimally invasive
- high throughput
- drug induced
- placebo controlled
- molecular dynamics simulations
- replacement therapy
- single cell
- study protocol
- solid state
- drug discovery