ABSTRACT
Introduction
First-generation therapeutics have improved clinical outcomes in patients infected with SARS-CoV-2. However, viral evolution has produced variants and subvariants capable of resisting many of these drugs and novel treatment strategies are urgently needed.
Areas covered
A corporate compound library screen identified ensitrelvir (formerly S-217622), a non-covalent, non-peptidic, orally bioavailable small-molecule protease inhibitor as a potential treatment for SARS-CoV-2. Ensitrelvir cleaves the active site of the 3C-like protease (3CLpro), which is conserved across SARS-CoV-2 variants and subvariants, with no human cell protease with similar specificity.
Expert opinion
Ensitrelvir demonstrates strong in vitro antiviral activity against the SARS-CoV-2 Omicron subvariants BA.4 and BA.5, which have driven new waves of infection throughout 2022, suggesting a potential therapeutic option for patients with COVID-19. This manuscript reviews what is known about ensitrelvir and explores how this drug may be used in the future to address the SARS-CoV-2 pandemic.
Article highlights
Ensitrelvir as an orally bioavailable small molecule with in vitro activity against a wide variety of SARS-CoV-2 variants and subvariants
Ensitrelvir has a strong affinity for the SARS-CoV-2 3C-like protease (3CLpro) without a similar target in humans.
Ensitrelvir demonstrates high in vitro activity against currently circulating SARS-CoV-2 Omicron subvariants BA.2.75, BA.4, and BA.5 with antiviral potency in preclinical testing similar to its potency against other existing variants.
Upcoming clinical research will define the potential role of ensitrelvir as a therapeutic agent for patients with COVID-19
Declaration of interest
The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
Reviewer disclosures
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.