Virus World

Drugmaker Pfizer said Friday its experimental pill designed to fight coronavirus reduced the risk of hospitalization and death for high-risk patients taking part in a trial of the drug.  The company hopes it can eventually offer the pill, given in combination with an older antiviral drug called ritonavir, to people to take at home before they get sick enough to go to the hospital. A so-called interim analysis -- done before the trial was scheduled to end -- showed an 89% reduction in the risk of hospitalization or death from Covid-19 if patients got it soon enough, the company said.  Pfizer released the results in a news release and did not provide scientists to discuss the data ahead of release. The data has not been peer reviewed or published. The company says it will share more specifics in a peer-reviewed paper and in its submission to the US Food and Drug Administration.  On CNN New Day on Friday, Pfizer CEO Albert Bourla said the company planned to submit data to regulators as soon as possible, maybe before Thanksgiving. The company has been testing the drug in adults with Covid-19 who are considered at high risk of progressing to severe illness. The volunteers have been randomly given either the pill combination or a placebo within three days or five days of their symptoms starting. The pill, called Paxlovid and its experimental name, PF-07321332, is what's known as a protease inhibitor. It's designed to stop the virus from multiplying. Giving it along with ritonavir slows its breakdown in the body, the company said. Pfizer said 0.8% of patients who got the drug combination within three days were hospitalized within four weeks -- three out of 389 patients -- compared to 7% of patients who got placebos, or 27 out of 385. And seven of those who got placebos died, Pfizer said. No one who got the treatment died within a month.

Vaccines and drugs have helped reduce disease severity and blunt the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, ongoing virus transmission, continuous evolution, and increasing selective pressures have the potential to yield viral variants capable of resisting these interventions. Here, we investigate the susceptibility of natural variants of the main protease [Mpro; 3C-like protease (3CLpro)] of SARS-CoV-2 to protease inhibitors. Multiple single amino acid changes in Mpro confer resistance to nirmatrelvir (the active component of Paxlovid). An additional clinical-stage inhibitor, ensitrelvir (Xocova), shows a different resistance mutation profile.

Importantly, phylogenetic analyses indicate that several of these resistant variants have pre-existed the introduction of these drugs into the human population and are capable of spreading. These results encourage the monitoring of resistance variants and the development of additional protease inhibitors and other antiviral drugs with different mechanisms of action and resistance profiles for combinatorial therapy.

Published in Science Advances (March 29, 2023)