Animal Model

Selected compound(s) effective against orthopoxviruses

Comments

Vaccinia keratitis

    Rabbit vaccinia keratitis

Polyinosinic-polycytidylic acid (Poly I:C) (36), ribavirin (112), Ara-A (68,111), Trifluorothymidine (69)

All compounds applied topically; Poly I:C only effective if given prophylactically

   Monkey vaccinia keratitis

Topical Interferon (92)

Non-lethal skin lesion models

   Rabbit vaccinia skin lesion

i.p. Polyacrylic acid (40), Ara-A (i.p. and topical) (76), Phosphonoacetic acid (topical) (54)

   Monkey vaccinia skin lesion

i.m. or i.v. interferon (128)

First dose given prior to vaccinia exposure

Tail lesion models

   Mouse vaccinia tail lesion

Isothiazole thiosemicarbazones (101), thiosemicarbazones (methisazone), murine interferion (39), polyacrylic acid (39), rifampicin (125), Ara-C (41), ribavirin (125)

   SCID mouse tail lesion

CDV (95)

Given s.c. prior to infection; prevented tail lesion development but all mice died from generalized viral infections

Encephalitis models

   Intracerebral inoculation of mice with

     Rabbitpox

Thiosemicarbazones (113)

   Intracerebral inoculation of mice with vaccinia

p.o., i.p., s.c thiosemicarbazones (84,101,113, 123, 124); p.o. or i.p. Ara-A (113)

   Intracerebral inoculation of mice with variola

Thiosemicarbazones (101)

Respiratory infection models

   Intranasal/aerosolized cowpox in mice

CDV (s.c.)(12), ribavirin followed by CDV (115), Lipid analogs of CDV (p.o.) (97), aerosolized CDV (11,105)

CDV effective if given as late as 4 days after infection

   Aerosolized monkeypox in monkeys

CDV (i.v.)

   Intranasal rabbitpox in rabbits

Isothiazole thiosemicarbazones (p.o.) (101)

   Intranasal vaccinia in mice

Thiosemicarbazones (63), CDV, Lipid analogs of CDV (p.o.) (97), imatinib mesylate (104)

CDV effective if given a day after infection

   Intranasal ectromelia in mice

Lipid analogs of CDV (p.o.) (97)

Lethal infection in immunocompromised mice

   Intracutaneous vaccinia infection in athymic

      mice (progressive vaccinia model)

Topical CDV, CDV (s.c.) (96)

Topical treatment was effective if given 2 days post-infection

   Intravenous vaccinia infection in mice given

     anti-thymocyte treatment

Ara-A (i.p.) (133)

   Intranasal cowpox infection of SCID mice

CDV (s.c.) (12)

   Vaccinia infection of SCID mice via

     intravenous, intranasal, or intraperitoneal

     routes

CDV (s.c.) (95), 5-Iodo-dUrd (s.c.) (94)

Prolongation of life occurred with antiviral therapy, but all eventually died from viral infection

   Vaccinia infection in mice given

     cyclophosphamide immunosuppression

Topical CDV (117)