How Pfizer scientists transformed an old drug lead into a COVID-19 antiviral
Behind the scenes of the medicinal chemistry campaign that led to the pill Paxlovid
But with its peptide-like structure, PF-00835231 is rich in hydrogen bond donors. It has five of them, and they give the molecule a polar surface area that traps it in the gut if swallowed. This means the molecule must be administered intravenously—something that can typically only be done in a hospital setting. Pfizer scientists wanted an antiviral pill that people could take at the first signs of infection, long before they had to go to the hospital.
To make their antiviral candidate Paxlovid, the team combined PF-07321332 with the HIV antiviral ritonavir. Owen says this approach was one the researchers thought they might have to take from the beginning of the project. Ritonavir has no activity against SARS-CoV-2 but does bind to metabolizing enzymes, thereby preventing PF-07321332 from being broken down before it has done its job mucking up the virus’s main protease.
中文的第九版诊疗手册里是写的是paxlovid 等于300mgPF-07321332+100mg利托那韦Ritonavir一起服用，我本来还在想这不是音译啊，原来paxlovid就没有翻译过来。
In 2003, researchers at the company developed an antiviral, known as PF-00835231, that could block the main protease of a coronavirus that emerged in 2002 and causes severe acute respiratory syndrome (SARS). But by the time they were ready to test it in patients, the SARS outbreak had been contained. PF-00835231 is structurally similar to a peptide that binds within SARS’s main protease. That binding site in SARS is identical to the one in SARS-CoV-2, so Pfizer researchers thought the molecule could work against the new virus. Tests showed they were right.