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S-892216 is an investigational, second-generation small molecule inhibitor targeting the 3C-like protease (3CLpro, also known as main protease or Mpro) of SARS-CoV-2. It is being developed by Shionogi for both prophylaxis and treatment of COVID-19. The drug has demonstrated strong *in vitro* and *in vivo* antiviral activity against multiple SARS-CoV-2 variants, including Omicron, with higher potency than currently approved 3CLpro inhibitors. S-892216 is being formulated as both a long-acting injectable for pre-exposure prophylaxis—particularly aimed at immunocompromised populations—and as an oral tablet for treatment. Preclinical studies show that it effectively reduces viral titers and lung inflammation at lower doses compared to other antivirals like ensitrelvir and nirmatrelvir[1][2][3][4][5].
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