Summary of histologic findings for placebo treated NHPs that met study endpoint before end of study.

Summary of histologic findings for placebo treated NHPs that met study endpoint before end of study.</p

The specificity of variola virus-specific RNA in situ hybridization (ISH).

A) variola virus (VARV) RNA was detected in the tongue tissue of a cynomolgus macaque, (placebo-treated #9) that succumbed to intravenous exposure of VARV using RNA ISH. B-C.) VARV RNA was undetectable in the lung tissue of a cynomolgus macaque that succumbed to aerosol exposure MPX virus using VARV-specific ISH (B), in which MPXV RNA was readily detected by MPXV-specific ISH (C).</p

Transmission electron micrographs of VARV infected, placebo-treated NHP haired skin.

Panels A, B, C all reveal flaking epidermis and disorganized dermal skin layers in three euthanized variola infected, placebo-treated non-human primates. Panels A’, B’, and C’ are higher magnification images of the boxed regions in panels A, B, and C, respectively, revealing the presence of VARV. Immature (5C’, white asterisk) and mature virions are evident. Brick-shaped, enveloped mature (black asterisk) and mature virions with bar-bell shaped cores (arrowheads) are readily visible. Inset in A’ shows the dimensions (~ 139nm X 246nm) of one mature virion. Superficial bacteria are also evident (arrows) in panels A and C’ (arrows). A’, B’, C’ scalebar = 500nm.</p

Variola-infected, placebo treated NHP x days post infection.

Haired skin, pox lesions. A: (H&E, 4x) Proliferative and necrotizing dermatitis. B: (IHC, 4x) Viral antigen is present within epithelial cells at the edge of the pox lesion. C: (H&E 20x) Higher magnification of A, Necrotic debris and superficial serocellular crust. D: (IHC, 40x) Viral antigen in epithelial cells. E: (40x/100x) Higher magnification of A, Pyknotic and karyorrhectic (necrotic) debris with intracytoplasmic inclusions (arrowhead; inset, higher magnification of black box) and ballooning degeneration (arrow) as well as surface colonies of bacteria. F: (IHC, 60x) Viral antigen in epithelial cells.</p

Skin lesions observed, maximum viremia, time to maximum viremia, and survival by tecovirimat treatment day.

Skin lesions observed, maximum viremia, time to maximum viremia, and survival by tecovirimat treatment day.</p

Summary of histologic findings for placebo and tecovirimat treated NHPs that survived to end of study by tecovirimat treatment group.

Summary of histologic findings for placebo and tecovirimat treated NHPs that survived to end of study by tecovirimat treatment group.</p

Variola-infected, placebo treated NHPs. Multifocal proliferative and necrotizing dermatitis (pox lesions).

A) Facial skin (13 days post infection); B) Abdominal skin, left inner thigh, and scrotum (7 days post infection); C) Glabrous skin, left palm: multifocal proliferative dermatitis (7 days post infection); D) Glabrous skin, left palm: multifocal healed lesions with depigmentation (29 days post infection).</p