Upamostat for COVID-19

Context: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first identified in Wuhan, China. From the outset, this highly contagious and dangerous illness posed significant risks and challenges for global healthcare systems and populations. Scientists and healthcare professionals worldwide have been striving to develop effective treatments for severe acute respiratory SARS-CoV-2 infection, employing both pre-existing and innovative approaches. However, a specific drug targeted explicitly against COVID-19 remains elusive. Despite the reduced prevalence of severe cases and the predominance of the SARS-CoV-2 Omicron variant, COVID-19 continues to pose significant risks, particularly for polymorbid patient groups. This review focuses on the potential antiviral effects of promising new drugs, including ensitrelvir, clazakizumab, upamostat, and others. Evidence Acquisition: An analytical review was conducted using the Scopus, PubMed, EMBASE, ScienceDirect, and Google Scholar databases for publications related to promising drugs against SARS-CoV-2, their mechanisms of action, and potential therapeutic effects up to November 2024. Selection criteria included: (1) Free-text availability; (2) English language; (3) relevance to the publication's theme a total of 104 articles were initially selected. Of these, 27 articles were excluded for not meeting the free-text criterion, 14 were excluded due to language incompatibility, and 28 were excluded for thematic irrelevance. Ultimately, data from 35 articles were analyzed and summarized for this review. Results: Thirty-five scientific studies were reviewed to describe current paradigms and emerging concepts in SARS-CoV-2 treatment. Current drugs with proven efficacy include: (1) Combined monoclonal antibodies targeting the S-protein (casirivimab/imdevimab); (2) monoclonal antibody preparations against the S-protein (pemivibart; vilobelimab); (3) viral replication inhibitors (molnupiravir); (4) protease inhibitors (nirmatrelvir/ritonavir); (5) immunosuppressants (dexamethasone; tocilizumab). The review also highlights drugs under development targeting traditional pathways [e.g., viral protease, interleukin-6 (IL-6)] and those aimed at novel mechanisms (e.g., antigalectin-3; adhesion blockers). Conclusions: Although numerous drug effects and potential drug combinations for COVID-19 have been described, limited clinical trials and research focus on identifying novel treatment approaches. Comprehensive investigations are needed to assess and evaluate the risks of different treatment strategies, minimizing potential short- and long-term complications for patients. Such advancements will pave the way for more optimal and effective medical treatment of COVID-19.