Phloretin for COVID-19

Phloretin may be beneficial for COVID-19 according to the studies below. COVID-19 involves the interplay of 500+ 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 phloretin in detail.
Ataya et al., Identification of polyphenols as novel neuropilin-1 cendR pocket inhibitors to block SARS-CoV-2 entry and enhance variant resistance, PLOS One, doi:10.1371/journal.pone.0345051
Neuropilin-1 (NRP-1) functions as an essential co-receptor for SARS-CoV-2, facilitating viral entry by binding the spike protein’s C-end rule (CendR) motif in its b1 domain, yet it has received less attention than ACE2 in therapeutic development. This in silico study evaluates plant-derived polyphenols as potential selective inhibitors of the NRP-1 CendR pocket to disrupt SARS-CoV-2 engagement, addressing limitations of synthetic inhibitors like EG01377, which exhibit modest affinity (−5.83 kcal/mol) and potential off-target risks. High-throughput molecular docking of 10,000 phytochemicals using AutoDock Vina identified 10 polyphenols with binding affinities ranging from −9.87 to −6.63 kcal/mol, led by 6“-O-acetyldaidzin (-9.87 kcal/mol) and phloretin (-8.64 kcal/mol), forming stable hydrogen bonds and π-cation interactions with critical residues (e.g., THR-401, GLU-367 for 6”-O-acetyldaidzin; PRO-311, ILE-400 for phloretin), as visualized in Discovery Studio. Notably, four of the top inhibitors are isoflavonoid derivatives, highlighting a chemical class enrichment. Molecular dynamics simulations over 100 ns using Desmond indicated moderate complex stability (RMSD: 0.6–3.8 Å; RMSF <0.5 Å at binding site ). ADMET-Tox profiling via SwissADME and ProTox-II revealed drug-like properties, including high gastrointestinal absorption (>70% for leads) and low toxicity (classes 4–5), though 6”-O-acetyldaidzin shows limited bioavailability due to its high H-bond acceptor count (10) and large size, suggesting need for formulation optimization. The NRP-1 b1 homology model, built with SWISS-MODEL, exhibited high fidelity (GMQE: 0.79; Ramachandran favored regions: 90.3% ). This focused computational screening of polyphenols against NRP-1 complements prior studies and identifies candidates for experimental validation as potential SARS-CoV-2 inhibitors. Limitations include the in silico nature, and lack of membrane/sialic acid models, necessitating in vitro and in vivo testing against SARS-CoV-2 variants.
Okechukwu et al., Marine-Derived Bioactive Metabolites as a Potential Therapeutic Intervention in Managing Viral Diseases: Insights from the SARS-CoV-2 In Silico and Pre-Clinical Studies, Pharmaceuticals, doi:10.3390/ph17030328
Worldwide urbanization and subsequent migration have accelerated the emergence and spread of diverse novel human diseases. Among them, diseases caused by viruses could result in epidemics, typified by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which hit the globe towards the end of December 2019. The global battle against SARS-CoV-2 has reignited interest in finding alternative treatments for viral infections. The marine world offers a large repository of diverse and unique bioactive compounds. Over the years, many antiviral compounds from marine organisms have been isolated and tested in vitro and in vivo. However, given the increasing need for alternative treatment, in silico analysis appears to provide a time- and cost-effective approach to identifying the potential antiviral compounds from the vast pool of natural metabolites isolated from marine organisms. In this perspective review, we discuss marine-derived bioactive metabolites as potential therapeutics for all known disease-causing viruses including the SARS-CoV-2. We demonstrate the efficacy of marine-derived bioactive metabolites in the context of various antiviral activities and their in silico, in vitro, and in vivo capacities.