Boosted Tecovirimat Injection for Orthopoxvirus Infection Therapy

Since 2022, global mpox outbreaks have resulted in 172 510 confirmed cases and 462 deaths as of October 31, 2025. Tecovirimat, a small-molecule therapeutic agent for orthopoxvirus infections (e.g., smallpox and mpox), is clinically limited owing to its poor solubility. A novel tecovirimat formulation was developed and characterized using scanning electron microscopy, X-ray powder diffraction, Fourier-transform infrared spectroscopy, and stability assessments. The antiviral activity of tecovirimat against orthopoxvirus was evaluated using cytopathic effect inhibition assays. Safety evaluations included: ① active systemic anaphylaxis and vascular irritation tests in guinea pigs and rabbits, respectively, evaluated using scoring systems and histopathological examinations; ② visual assessment of hemolytic activity in red blood cells; and ③ repeated-dose toxicity evaluation in cynomolgus monkeys (14-d administration followed by a 28-d recovery period). The novel formulation enhanced the aqueous solubility of tecovirimat to 50 mg∙mL –1 . The lyophilized powder formulation 5 (LP5) exhibited exceptional stability under high-temperature, high-humidity, and photolytic conditions and maintained favorable physicochemical properties after 90 days of storage at 40 °C and 75% relative humidity (RH). Furthermore, safety assessments revealed no concerns regarding allergic reaction, irritation, hemolysis, or toxicity in repeated-dose studies. These findings demonstrate that the novel tecovirimat formulation is a stable, safe, and promising candidate for industrial development and clinical applications.