Boosted Tecovirimat Injection for Orthopoxvirus Infection Therapy

Yaqin Sun; Cheng Niu; Guangyan Sun; Xinyuan Zhao; Suyue Zhang; Zaiwei Zong; Wei Wang; Feiqiang Chen; Tianyi Fan; Na Liu; Shaoting Qiu; Yani Li; Xupeng Wei; Yunzheng Yan; Shuyuan Pan; Wu Zhong; Yuntao Zhang; Song Li

doi:10.1016/j.eng.2026.02.007

Engineering ›› :202602007 DOI: 10.1016/j.eng.2026.02.007

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Boosted Tecovirimat Injection for Orthopoxvirus Infection Therapy

Yaqin Sun ^a^,^d^,^#
, Cheng Niu ^a^,^d^,^#
, Guangyan Sun ^a^,^d^,^#
, Xinyuan Zhao ^a^,^d
, Suyue Zhang ^a
, Zaiwei Zong
, Wei Wang ^a^,^d
, Feiqiang Chen ^b
, Tianyi Fan ^a
, Na Liu ^a
, Shaoting Qiu ^a^,^d
, Yani Li ^a
, Xupeng Wei ^a
, Yunzheng Yan ^a^,^d^,^*
, Shuyuan Pan ^a^,^d^,^*
, Wu Zhong ^c^,^*
, Yuntao Zhang ^d^,^e^,^*
, Song Li ^c

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Abstract

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.

Keywords

Tecovirimat / Formulation / Antiviral / Industrial development / Orthopoxvirus

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Yaqin Sun, Cheng Niu, Guangyan Sun, Xinyuan Zhao, Suyue Zhang, Zaiwei Zong, Wei Wang, Feiqiang Chen, Tianyi Fan, Na Liu, Shaoting Qiu, Yani Li, Xupeng Wei, Yunzheng Yan, Shuyuan Pan, Wu Zhong, Yuntao Zhang, Song Li. Boosted Tecovirimat Injection for Orthopoxvirus Infection Therapy. Engineering 202602007 DOI:10.1016/j.eng.2026.02.007

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