[1] As an author, he was known for promoting a three-drug combination of hydroxychloroquine, zinc sulfate, and azithromycin as part of an experimental outpatient treatment for COVID-19 that he called the Zelenko Protocol.

[2][3] On March 23, 2020, Zelenko published an open letter to U.S. president Donald Trump where he claimed to have successfully treated hundreds of COVID-19 patients with a five-day course of his protocol.

Zelenko's treatment protocol quickly gained notoriety, with several right-wing media figures and various Trump administration officials promoting it, including Rudy Giuliani and then-White House Chief of Staff Mark Meadows, despite cautionary messages from health experts.

[7][8] On March 21, 2020, Zelenko posted a video to YouTube and Facebook addressed to U.S. president Donald Trump, in which he claimed to have successfully tested an experimental treatment for COVID-19 on hundreds of patients with coronavirus-like symptoms.

[4] He described the treatment as a three-drug combination consisting of the anti-malarial medication hydroxychloroquine, the antibiotic azithromycin, and zinc sulfate,[9] and posted an open letter to Trump with similar claims two days later.

[11] In March 2020, Alex Kasprak, a science writer for Snopes, noted that since Zelenko did not describe his study design nor publish any data, his claims were unverifiable.

Fact-checkers noted the lack of scientific support for Zelenko's claims of Z-Stack's ingredients boosting immunity, killing the virus that causes COVID-19, and preventing hospitalization.

[23] In April 2020, Zelenko presented a lecture over Zoom to a group of physicians, in which he alleged that the Food and Drug Administration (FDA) had granted approval to a clinical trial he was helping organize.