sangivamycin (TNX-3500) / OyaGen, National Institute of Allergy and Infectious Diseases, Tonix - LARVOL DELTA

Structural insights into the catalytic cycle of G protein-coupled receptor kinase 5 and a possible regulatory site for potassium ion. (PubMed, J Biol Chem) - "Although K+ significantly stabilizes GRK5 in its closed, near active conformation, potassium citrate and KCl inhibit kinase activity just as potently as sodium citrate and NaCl, respectively, suggesting that K+ traps a closed conformation compatible with Sgv/AMP but incompatible with ATP, thereby inhibiting the catalytic cycle. Thus, changes in K+ concentration could play a regulatory role for GRK5 in scenarios where activated GPCRs are coupled to G protein-responsive potassium channels."

Journal

Sangivamycin is preferentially incorporated into viral RNA by the SARS-CoV-2 polymerase. (PubMed, Antiviral Res) - "In contrast, host mRNA, affinity purified from the same infected and treated cells, contained little or no S. Sangivamycin triphosphate (STP) was synthesized to evaluate its incorporation into RNA by recombinant SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) under defined in vitro conditions. SARS-CoV-2 RdRp showed that S was not a chain terminator and S containing oligonucleotides templated as A. Though the antiviral mechanism remains to be determined, the data suggests that SARS-CoV-2 RdRp incorporates STP into SARS-CoV-2 RNA, which does not significantly impair viral RNA synthesis or the mutation rate."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Sangivamycin is highly effective against SARS-CoV-2 in vitro and has favorable drug properties. (PubMed, JCI Insight) - "Sangivamycin suppressed SARS-CoV-2 replication with greater efficacy than remdesivir (another broad-spectrum nucleoside analog)...Sangivamycin may also have the ability to help combat drug-resistant or vaccine-escaping SARS-CoV-2 variants since it is antivirally active against several tested variants. Our results support the pursuit of sangivamycin for further preclinical and clinical development as a potential coronavirus disease 2019 (COVID-19) therapeutic."

Journal • Preclinical • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

"$TNXP Tonix Pharmaceuticals Announces Publication of Paper on Antiviral SARS-CoV-2 Inhibitor, TNX-3500, in JCI Insight https://t.co/wQ1UFVN3PH" (@stock_titan)

Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Putative role of natural products as Protein Kinase C modulator in different disease conditions. (PubMed, Daru) - "Based on the comprehensive literature survey, it could be concluded that various natural products can regulate PKC activity during disease progression. However, extensive research is needed to circumvent the challenge of isoform specific regulation of PKC by natural products."

Journal • Review • CNS Disorders • Heart Failure • Oncology

Tonix Pharmaceuticals Enters into Exclusive Worldwide Licensing Agreement with OyaGen to Develop Antiviral SARS-CoV-2 Inhibitor, TNX-3500, for the Treatment of COVID-19 (GlobeNewswire) - "Tonix Pharmaceuticals Holding Corp...and OyaGen, Inc....announced today an exclusive worldwide licensing agreement for an antiviral inhibitor of SARS-CoV-2, TNX-3500 (sangivamycin, formerly OYA1), for the treatment of COVID-19 and potentially other viral disorders....Under the terms of the agreement, Tonix has been granted an exclusive license from OyaGen for technology and patents related to TNX-3500 and other related compounds. Tonix will conduct further studies to test the safety and efficacy of TNX-3500 in treating COVID-19 as necessary to support regulatory approval."

Licensing / partnership • Infectious Disease • Novel Coronavirus Disease