Looking Ahead: An Effective Oral Drug for Treatment of COVID-19

The three worst pandemics in known human history were the bubonic plague in the 14th century, influenza in 1918, and the acquired immune deficiency syndrome (AIDS) that was first recognized in 1981. Influenza killed 50 million people, AIDS has killed 35 million, and COVID-19 has killed about 5 million, so far. Now it appears that offshoots of the antiretroviral drugs that turned HIV infection into a manageable chronic disease may be the answer to our prayers for an accessible oral drug that could effectively treat COVID-19.

Molnupiravir, an oral prodrug of a synthetic nucleoside derivative developed by Merck and Ridgeway, is on the FDA’s docket for an Emergency Use Authorization, but its somewhat modest effectiveness and potential mutagenicity are concerning. An advance-release article on this subject was published in our October 4 issue and an update will be out soon.

Paxlovid, a mixture of 2 protease inhibitors manufactured by Pfizer, is also given orally. According to the manufacturer, when given to high-risk patients within 3-5 days of symptom onset in a randomized, double-blind trial, it was highly effective in preventing hospitalization and death from COVID-19. Ten deaths occurred in placebo-treated patients compared to none among those treated with the drug. The limited clinical data available to date are summarized in our Treatments Considered for COVID-19 table.

An article in the August 21 issue of Current Opinions in Virology (2021; 49:36) described the long, difficult path to discovery of the Pfizer drug. FDA-approved HIV protease inhibitors are not effective against SARS-CoV-2. Ritonavir, which is FDA-approved, is the second protease inhibitor in Paxlovid, but it functions only to slow the metabolism of PF-07321332, the protease inhibitor that inhibits replication of the virus.

Of course, a drug that inhibits replication must be taken while the virus is still replicating, and the earlier, the better. To accomplish that, we need a reliable, accessible, rapid diagnostic test. The Medical Letter’s free COVID-19 resources include a table listing over-the-counter at-home diagnostic tests for COVID-19, their accuracy, and their cost, but their lack of availability in the US has been a problem. Some editorials have suggested that the US government should provide the tests to everyone free of charge, as other governments have done. That would certainly help.

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