WU-04 for COVID-19

c19early.org

COVID-19 Treatment Clinical Evidence

COVID-19 involves the interplay of 400+ viral and host proteins and factors, providing many therapeutic targets. c19early analyzes 6,000+ studies for 210+ treatments—over 17 million hours of research. Only three high-profit early treatments are approved in the US. In reality, many treatments reduce risk, with 25 low-cost treatments approved across 163 countries.

Naso/oropharyngeal treatment Effective Treatment directly to the primary source of initial infection.
Healthy lifestyles Protective Exercise, sunlight, a healthy diet, and good sleep all reduce risk.
Immune support Effective Vitamins A, C, D, and zinc show reduced risk, as with other viruses.
Thermotherapy Effective Methods for increasing internal body temperature, enhancing immune system function.
Systemic agents Effective Many systemic agents reduce risk, and may be required when infection progresses.
High-profit systemic agents Conditional Effective, but with greater access and cost barriers.
Monoclonal antibodies Limited Utility Effective but rarely used—high cost, variant dependence, IV/SC admin.
Acetaminophen Harmful Increased risk of severe outcomes and mortality.
Remdesivir Harmful Increased mortality with longer followup. Increased kidney and liver injury, cardiac disorders.

WU-04 may be beneficial for COVID-19 according to the studies below. COVID-19 involves the interplay of 400+ viral and host proteins and factors providing many therapeutic targets. Scientists have proposed 11,000+ potential treatments. c19early.org analyzes 210+ treatments. We have not reviewed WU-04 in detail.

Studies suggesting benefit with WU-04

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 (M^pro), 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.