Researchers from the University of Hong Kong-China, Centre for Virology, Vaccinology and Therapeutics, Hong Kong Science and Technology Park-China, and The University of Hong Kong-Shenzhen Hospital, Shenzhen-China, have made a groundbreaking discovery in the fight against COVID-19. Their study has identified Alisol B 23-Acetate (AB23A), a natural compound found in Alisma orientalis, as a potential candidate for COVID-19 treatment. AB23A not only inhibits the entry of the coronavirus into cells but also suppresses proinflammatory T-cell responses. This discovery holds great promise in the ongoing battle against the virus.
COVID-19 has posed significant challenges since the emergence of SARS-CoV-2. Among the three major coronavirus outbreaks, including SARS and MERS, COVID-19 has proven to be the most devastating. The virus enters human cells by binding its spike protein to the ACE2 receptor. As different variants of SARS-CoV-2 continue to emerge, new challenges arise, such as increased antibody evasion and potential resistance to existing treatments.
Efforts to develop effective treatments for COVID-19 have faced obstacles. Initially, repurposed drugs showed mixed results, and IL-6 receptor inhibitors had limitations. Paxlovid, a protease inhibitor, raised concerns about viral rebound in Omicron variant infections. The rapid mutation rate of SARS-CoV-2 highlights the need for new therapeutic agents that can effectively combat the virus and its future variants.
Traditional Chinese Medicine (TCM) has a rich history in combating epidemic infectious diseases. Researchers have turned to TCM formulations for potential COVID-19 treatments in China. One such formulation is QingFei PaiDu (QFPD) Decoction, which contains various compounds with antiviral, anti-inflammatory, and immunomodulatory properties. Among these compounds, researchers identified Alisol B 23-Acetate (AB23A) as a potential candidate for COVID-19 treatment.
AB23A, a natural compound found in Alisma orientalis, has previously been recognized for its antibacterial, anti-inflammatory, and hepatoprotective properties. In screening tests, AB23A demonstrated inhibitory effects on various coronavirus species, including the Alpha, Delta, and Omicron variants. This broad-spectrum activity suggests that AB23A could be a potential pan-coronavirus inhibitor.
Further experiments explored how AB23A inhibits viral entry by blocking the binding of the virus’s spike protein to ACE2 receptors. The use of hydrogen/deuterium exchange (HDX) mass spectrometry provided insights into the molecular interactions between AB23A and ACE2. The results demonstrated that AB23A interacts with specific regions of ACE2 that are crucial for the ACE2-Spike protein interaction.
Encouraged by promising in vitro results, researchers tested AB23A’s efficacy in animal models. In hamsters and human ACE2 transgenic mice infected with SARS-CoV-2 and its variants, AB23A significantly reduced viral load, mitigated lung damage, and suppressed proinflammatory immune responses. AB23A also showed potential in mitigating inflammation by reducing superoxide and peroxynitrite levels, as well as proinflammatory cytokines. It inhibited the infiltration of immune cells in lung tissues.
While AB23A demonstrated potential cytotoxicity in vitro, acute toxicity studies in hamsters indicated its safety even at doses higher than the therapeutic dosage used in the study. However, further investigations are needed to explore the compound’s long-term safety and optimize its translational application.
In conclusion, the discovery of Alisol B 23-Acetate (AB23A) represents a significant breakthrough in the search for effective COVID-19 treatments. This natural compound exhibits broad-spectrum antiviral properties and potent anti-inflammatory effects. Its mechanisms of action include interference with the ACE2-Spike protein interaction and suppression of proinflammatory immune responses. AB23A’s safety profile and versatility against various coronavirus variants make it a promising therapeutic agent. Further research is needed to unlock its full potential and bring it closer to clinical application.