Alunacedase alfa

Alunacedase alfa (APN-01) is a soluble angiotensin-converting enzyme 2 (hrsACE2) with antiviral activity that reduces the competitive entry of SARS-CoV-2 into cell membranes bound to ACE2. alunacedase alfa mimics ACE2 in vivo and can be used to study novel coronavirus infections, pulmonary hypertension and acute lung injury. Alunacedase alfa mimics ACE2 in vivo and can be used to study novel coronavirus infections, pulmonary hypertension and acute lung injury.

SARS-CoV-2 spike glycoprotein:1.2 nM (Kd)

Alunacedase alfa exhibits high-affinity binding to the SARS-CoV-2 spike glycoprotein, with an estimated affinity of approximately 1.2 nM.[2]
Methods: The compound Alunacedase alfa was tested at a concentration gradient ranging from 0.01 to 1000 μg/mL. It was incubated with SARS-CoV-2 (USA-WA1/2020) at 37°C for 1 hour, then added to Vero E6 cells (MOI = 0.001) for further culture for 4 days. Cytopathic effect (CPE) and cell viability were assessed using the neutral red assay.
Results: Alunacedase alfa at 25 μg/mL completely neutralized SARS-CoV-2 and exhibited no cytotoxic effects on cells.[3]

Methods: Alunacedase alfa was administered intranasally at a dose of 100 μg per mouse once daily for 5 consecutive days. The experimental model consisted of BALB/c mice infected intranasally with 1×10⁵ TCID₅₀ of a mouse-adapted SARS-CoV-2 strain (maVie16). Outcomes assessed included body weight, body temperature, survival rate, and lung tissue weight.
Results: Alunacedase alfa resulted in 100% survival among infected mice, significantly alleviated weight loss and lung injury, and reduced lung tissue weight. [3]
Methods: Alunacedase alfa was administered in three dose groups: low (0.019 mg/L), medium (0.038 mg/L), and high (0.075 mg/L). Administration consisted of nebulization twice daily for 60 minutes, administered continuously for 14 days. The experimental model was Beagle dogs. Clinical signs, body weight, clinical pathology, histopathology, and toxicokinetic parameters were assessed.
Results: No significant toxicity was observed in any of the Alunacedase alfa dose groups, with no systemic or organ-specific damage; the highest dose of 0.075 mg/L was determined to be the NOAEL; systemic drug exposure was extremely low, and tolerability was excellent.[3]

Virus

Monoclonal

Unconjugated