Family Guy creator Seth MacFarlane has said it would be "troublingly dystopian" to have Oprah Winfrey running for president against Donald Trump in the next USA election.
For some of Winfrey's fans, a presidential run didn't seem far-fetched after her speech, with the topic quickly taking off on social media.
Mr Trump declared on Tuesday that he thinks he could beat Winfrey in a race to the White House.
Last fall Winfrey dismissed the notion of running for president.
"She lived, as we all have lived, too many in a culture broken by brutally powerful men", Winfrey said.
"I also know that after years of watching "The Oprah Show" you always have the right to change your mind".More news: 'Play our best:' Brady brushes off controversy, focuses on Titans
One of Ms Winfrey's closest friends said the media mogul and actress was "intrigued" by the possibility of running but was not considering it now.
"Oprah will be a lot of fun", Trump said Tuesday, noting that he knows Winfrey "very well" and appeared with his family on one of the final episodes of "The Oprah Winfrey Show". "If it means looking at one of these celebrities that have a moral core, that are compassion and intelligent, I think that people should look to where they can during these very, very hard times".
Speculation about a 2020 White House bid by Ms Winfrey blew up on social media and news outlets after her rousing "new day" speech.
Sanders was also asked whether she believed Winfrey was qualified to run for president.
A video of a past interview with Trump praising Winfrey has begun recirculating, showing the now-president revealing she'd be his top pick to be vice president. "So I probably made 17 versions of it, but then I felt like it was important to say something about her and let her speak".
Even Trump's daughter Ivanka endorsed Oprah's message, if not a political future, in a tweet Monday.More news: W&T Offshore, Inc. (WTI) Insider sold 167063 Shares
Trump himself has been accused of being a serial sexual predator by more than a dozen women.
"She's popular, she's brilliant, she's a wonderful woman", he said at the time. "I'd love to have Oprah".
Some political operatives think she has what it takes to be a viable presidential contender.
Allison Janney told ABC News, "I am all about Oprah 2020".
"She would be a serious candidate", said Jennifer Palmieri, former White House communications director under President Barack Obama and the communications director for Hillary Clinton's 2016 campaign.
As her longtime partner Stedman Graham watched from the audience, she told the story of a black woman from Alabama named Recy Taylor, who died at the age of 97 on December 28, 2017, and her fight for justice after her rape by six white men in 1944.More news: Wow, Looks Like Mark Wahlberg is a Pretty Slippery Snake
"I think lessons we all learned from watching Hillary's run, and how her ambition was unfavorably and unfairly viewed, coupled with Oprah's existing popularity, could give Oprah a strong start", Palmieri said.