ABX464 for the Treatment of SARS-CoV-2
The outbreak of COVID-19 caused by SARS-CoV-2 is still spreading around the world, and researchers all over the world have launched competition-like research. Creative Biolabs relies on its rich experience in the field of drug development, and also integrates all its capabilities to participate in this white war, providing researchers with powerful technical services to help humans overcome SARS-CoV-2.
SARS-CoV-2 is a single-stranded RNA enveloped virus that targets cells by a viral structural spike protein (S) that binds to the angiotensin converting enzyme 2 (ACE2) receptor. Moreover, the host's type 2 transmembrane serine protease TMPRSS2 promotes virus entry into cells through the S protein. Once inside the cell, the virus synthesizes polyproteins, encoding replicase-transcriptase complexes. The virus then synthesizes RNA through its RNA-dependent RNA polymerase. After the synthesis of structural proteins, the assembly and release of virus particles were completed. These life cycle steps of the virus provide potential targets for drug treatment. Promising drug targets include non-structural proteins (such as 3-chymotrypsin-like proteases, papain-like proteases, RNA-dependent RNA polymerase, etc). Other drug targets include components related to viral entry and immunomodulatory pathways.
ABX464 is an effective anti-HIV agent. ABX464 acts on stimulated peripheral blood mononuclear cells (PBMCs) and inhibits HIV-1 replication with IC50 of 0.1 μM to 0.5 μM. The researchers believe that ABX464 has potential triple effects on the treatment of COVID-19: antiviral, anti-inflammatory, and tissue repair. RT-qPCR evaluation found that ABX464 can inhibit the in vitro replication of SARS-CoV-2. Most patients with COVID-19 died of lung inflammation caused by viral replication or acute respiratory failure caused by long-term fibrosis. In addition, ABX464 also meets the strategic priorities of the new COVID-19 drugs required by the National Institutes of Health/Institute of Allergy and Infectious Diseases (NIH/NIAID): antiviral, anti-inflammatory, tissue repair, oral, and convenient once-daily administration. Specifically, ABX464 can splice non-coding RNA, LncRNA 205, by binding to the cap-binding protein complex (CBC), thereby producing miR-124. miR-124 is an effective anti-inflammatory small molecule ribonucleic acid, which can prevent the translation of various chemicals and cytokines in COVID-19 cytokine storm (including TNFα, IL-1β, G-CSF, IL-6, MCP-1, and IL-17). In addition, the replication of SARS-CoV-2 requires dynamin 2, a GTPase responsible for viral vesicle incision and cell penetration. Dynamin 2 is the target gene of miR-124, and the expression of miR-124 can inhibit the expression of dynamin 2.
Fig.1 ABX464 upregulates a single microRNA, the anti-inflammatory miR-124. (Vautrin, A and Manchon, L, 2019)
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