FGA145 for COVID-19

 FGA145 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 FGA145 in detail.
Atatreh et al., Exploring covalent inhibitors of SARS-CoV-2 main protease: from peptidomimetics to novel scaffolds, Journal of Enzyme Inhibition and Medicinal Chemistry, doi:10.1080/14756366.2025.2460045
Medrano et al., Peptidyl nitroalkene inhibitors of main protease rationalized by computational and crystallographic investigations as antivirals against SARS-CoV-2, Communications Chemistry, doi:10.1038/s42004-024-01104-7
AbstractThe coronavirus disease 2019 (COVID-19) pandemic continues to represent a global public health issue. The viral main protease (Mpro) represents one of the most attractive targets for the development of antiviral drugs. Herein we report peptidyl nitroalkenes exhibiting enzyme inhibitory activity against Mpro (Ki: 1–10 μM) good anti-SARS-CoV-2 infection activity in the low micromolar range (EC50: 1–12 μM) without significant toxicity. Additional kinetic studies of compounds FGA145, FGA146 and FGA147 show that all three compounds inhibit cathepsin L, denoting a possible multitarget effect of these compounds in the antiviral activity. Structural analysis shows the binding mode of FGA146 and FGA147 to the active site of the protein. Furthermore, our results illustrate that peptidyl nitroalkenes are effective covalent reversible inhibitors of the Mpro and cathepsin L, and that inhibitors FGA145, FGA146 and FGA147 prevent infection against SARS-CoV-2.
Medrano et al., Peptidyl Nitroalkene Inhibitors of Main Protease (Mpro) rationalized by Computational/Crystallographic Investigations as Antivirals against SARS-CoV-2, Research Square, doi:10.21203/rs.3.rs-2740892/v1
Abstract The coronavirus disease 2019 (COVID-19) pandemic continues to represent a global public health issue. The viral main protease (Mpro) represents one of the most attractive targets for the development of antiviral drugs. Herein we report peptidyl nitroalkenes exhibited enzyme inhibitory activity against Mpro (Ki: 1-10 micM) and three of them good anti-SARS-CoV-2 infection activity in the low micromolar range (EC50: 1-12 micM) without significant toxicity. Additional kinetic studies of compounds FGA145, FGA146 and FGA147 show that all three compounds inhibit Cathepsin L, denoting a possible multitarget effect of these compounds in the antiviral activity. QM/MM computer simulations assisted in the design and in elucidating the way of action. Finally, structural analysis shows, in agreement with the computer predictions, the binding mode of FGA146 and FGA147 to the active site of the protein. Our results illustrate that peptidyl nitroalkenes are potent covalent reversible inhibitors of the Mpro and cathepsin L, and that inhibitors FGA145, FGA146 and FGA147 prevent infection becoming promising drugs against SARS-CoV-2.