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FGA145 for COVID-19

FGA145 has been reported as potentially beneficial for treatment of COVID-19. We have not reviewed these studies. See all other treatments.
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.
Please send us corrections, updates, or comments. c19early involves the extraction of 100,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Treatments and other interventions are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. FLCCC and WCH provide treatment protocols.
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