Biology subjects

Ahmed-Belkacem, A.

Publications and source records attributed to Ahmed-Belkacem, A..

3 recordsLinked to original sources

bioRxiv2026

Bivalent CK2 Inhibition as a Potent Strategy Against SARS-CoV-2 and Other Coronaviruses

Protein kinase CK2 (CK2), a ubiquitously expressed serine/threonine kinase, has emerged as a key host factor exploited by several viruses, including Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we investigate the role of CK2 subunits in SARS-CoV-2 replication and evaluate the antiviral potential and broad-spectrum anti-coronavirus activity of two CK2 inhibitors: the previously described ATP-competitive inhibitor CX-4945 and a newly developed, highly selective bivalent inhibitor, AB668. The siRNA-mediated knockdown of CK2 subunits significantly reduced SARS-CoV-2 replication, highlighting its essential role in the viral lifecycle. Co-immunoprecipitation assays revealed that the SARS-CoV-2 nucleoprotein interacts with CK2. Furthermore, bio-layer interferometry assays demonstrated that the nucleoprotein specifically binds to the tetrameric CK2 holoenzyme (CK22{beta}2) but not to individual CK2 or CK2{beta} subunits. Pharmacological inhibition of CK2 with AB668 exhibited potent antiviral activity, significantly reducing viral replication by targeting a pre-replicative or RNA-replicative step of the viral life cycle. Importantly, AB668 displayed broad-spectrum antiviral activity, effectively inhibiting both HCoV-OC43 ({beta}-CoV) and HCoV-229E (-CoV). In summary, our findings establish CK2 as a critical host factor for SARS-CoV-2 replication and identify AB668 as a promising candidate for broad-spectrum antiviral therapy. With its high selectivity, minimized off-target effects, and efficacy against multiple coronaviruses, AB668 represents a valuable chemobiological and therapeutic tool.

microbiology↗

bioRxiv2025

Identification and characterization of a non-peptidic cyclophilin ligand with antiviral activity against feline and porcine α-coronaviruses.

Coronaviruses (CoVs) are emerging pathogens that have been extensively studied over the last 20 years and can cause acute respiratory diseases in humans, as exemplified by the SARS-CoV-2 pandemic. Coronaviruses are also known for their importance in veterinary medicine, being responsible for severe pathologies in pets and livestock. These include Feline Infectious Peritonitis Virus (FIPV), which causes a fatal disease in cats. In livestock, porcine coronaviruses such as Transmissible Gastroenteritis Virus (TGEV) and Porcine Epidemic Diarrhoea Virus (PEDV) are the causative agents of an acute enteric disease in piglets with a high mortality rate and a significant impact on the pork industry. In addition, animal coronaviruses may represent a zoonotic reservoir. Therefore, efficient antiviral strategies are required to inhibit the multiplication of coronaviruses infecting various animal species. Here, we synthesized 20 small-molecule ligands that target cyclophilins, a family of cellular chaperons hijacked by several viruses including CoVs. We screened their antiviral activity against feline and porcine alpha-CoVs, and identified a compound, F83233, as a potent inhibitor of FIPV, TGEV and PEDV replication at micromolar concentrations that was effective in feline, porcine and simian cells. As cyclophilins are highly conserved among mammals, F83233 could be a promising antiviral to treat different animal and zoonotic coronaviruses.

microbiology↗

bioRxiv2019

Hepatitis C virus regulates its replication by maturing miR-122 through Akt-dependent phosphorylation of KSRP

The liver-specific micro-RNA-122 (miR-122) is required for the replication of hepatitis C virus (HCV). The direct interaction between miR-122 and the 5 untranslated region of the HCV genome promotes viral replication and protects HCV RNA from degradation. Because HCV RNA is its own substrate for replication, infected cells are submitted to the sequestration of increasing levels of miR-122 and to global de-repression of host miR-122 mRNA targets. Whether and how HCV regulates miR-122 maturation to create an environment favorable to its replication remains unexplored. We discovered that Akt-dependent phosphorylation of KSRP host protein at Serine residue 193 is essential for miR-122 maturation in hepatocytes. Moreover, we showed the existence of a reciprocal regulation loop where HCV replication can modulate the proviral effect mediated by KSRP-dependent maturation of miR-122. These data support a mechanism by which HCV regulates the expression of miR-122 by hijacking KSRP, thereby fueling its own replication.

microbiology↗