WU-04 for COVID-19

 WU-04 has been reported as potentially beneficial for COVID-19 in the following studies.
COVID-19 involves the interplay of 350+ viral and host proteins and factors providing many therapeutic targets. Scientists have proposed 10,000+ potential treatments. c19early.org analyzes 200+ treatments. We have not reviewed WU-04 in detail.
Jing et al., Optimization of SARS-CoV-2 Mpro Inhibitors by a Structure-Based Multilevel Virtual Screening Method, International Journal of Molecular Sciences, doi:10.3390/ijms26020670
With the aim of developing novel anti-SARS-CoV-2 drugs to address the ongoing evolution and emergence of drug-resistant strains, the reported SARS-CoV-2 Mpro inhibitor WU-04 was selected as a lead to find novel, highly potent, and broad-spectrum inhibitors. Using a fragment-based multilevel virtual screening strategy, 15 hit compounds were identified and subsequently synthesized. Among them, A5 (IC50 = 1.05 μM), A6 (IC50 = 1.08 μM), and A9 (IC50 = 0.154 μM) demonstrated potent SARS-CoV-2 Mpro inhibition comparable to or slightly weaker than WU-04. Antiviral activity evaluations revealed that compound A9 exhibited the strongest antiviral activity with an EC50 value of 0.18 μM, quite comparable to the marketed drug Nirmatrelvir (EC50 = 0.123 μM) and inferior to WU-04 (EC50 = 0.042 μM). Molecular dynamics simulations elucidated the key interactions between compounds A5, A6, A9, and the binding pocket of SARS-CoV-2 Mpro, providing valuable insights into their mechanisms of action. These findings identify compound A9 as a promising lead for anti-SARS-CoV-2 drug development.
Yang et al., Progress in Research on Inhibitors Targeting SARS-CoV-2 Main Protease (Mpro), ACS Omega, doi:10.1021/acsomega.4c03023
Yevsieieva et al., Main and papain-like proteases as prospective targets for pharmacological treatment of coronavirus SARS-CoV-2, RSC Advances, doi:10.1039/d3ra06479d
The review outlines coronavirus SARS-CoV-2 morphology, life cycle, and essential proteins, focusing on a design strategy for dual-acting inhibitors for PLpro and Mpro proteases.