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Vaccinia virus inhibitors as a paradigm for the chemotherapy of poxvirus infections.
Clin Microbiol Rev 2001; 14(2):382-97CM

Abstract

Poxviruses continue to pose a major threat to human health. Monkeypox is endemic in central Africa, and the discontinuation of the vaccination (with vaccinia virus) has rendered most humans vulnerable to variola virus, the etiologic agent of smallpox, should this virus be used in biological warfare or terrorism. However, a large variety of compounds have been described that are potent inhibitors of vaccinia virus replication and could be expected to be active against other poxviruses as well. These compounds could be grouped in different classes: (i) IMP dehydrogenase inhibitors (e.g., EICAR); (ii) SAH hydrolase inhibitors (e.g., 5'-noraristeromycin, 3-deazaneplanocin A, and various neplanocin A derivatives); (iii) OMP decarboxylase inhibitors (e.g., pyrazofurin) and CTP synthetase inhibitors (e.g., cyclopentenyl cytosine); (iv) thymidylate synthase inhibitors (e.g., 5-substituted 2'-deoxyuridines); (v) nucleoside analogues that are targeted at viral DNA synthesis (e.g., Ara-A); (vi) acyclic nucleoside phosphonates [e.g., (S)-HPMPA and (S)-HPMPC (cidofovir)]; and (vii) polyanionic substances (e.g., polyacrylic acid). All these compounds could be considered potential candidate drugs for the therapy and prophylaxis of poxvirus infections at large. Some of these compounds, in particular polyacrylic acid and cidofovir, were found to generate, on single-dose administration, a long-lasting protective efficacy against vaccinia virus infection in vivo. Cidofovir, which has been approved for the treatment of cytomegalovirus retinitis in immunocompromised patients, was also found to protect mice, again when given as a single dose, against a lethal aerosolized or intranasal cowpox virus challenge. In a biological warfare scenario, it would be advantageous to be able to use a single treatment for an individual exposed to an aerosolized poxvirus. Cidofovir thus holds great promise for treating human smallpox, monkeypox, and other poxvirus infections. Anecdotal experience points to the efficacy of cidofovir in the treatment of the poxvirus infections molluscum contagiosum and orf (ecthyma contagiosum) in immunosuppressed patients.

Authors+Show Affiliations

Division of Virology and Chemotherapy, Department of Microbiology and Immunology, Rega Institute for Medical Research, K.U. Leuven, B-3000 Leuven, Belgium. erik.declercq@rega.kuleuven.ac.be

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

11292644

Citation

De Clercq, E. "Vaccinia Virus Inhibitors as a Paradigm for the Chemotherapy of Poxvirus Infections." Clinical Microbiology Reviews, vol. 14, no. 2, 2001, pp. 382-97.
De Clercq E. Vaccinia virus inhibitors as a paradigm for the chemotherapy of poxvirus infections. Clin Microbiol Rev. 2001;14(2):382-97.
De Clercq, E. (2001). Vaccinia virus inhibitors as a paradigm for the chemotherapy of poxvirus infections. Clinical Microbiology Reviews, 14(2), pp. 382-97.
De Clercq E. Vaccinia Virus Inhibitors as a Paradigm for the Chemotherapy of Poxvirus Infections. Clin Microbiol Rev. 2001;14(2):382-97. PubMed PMID: 11292644.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Vaccinia virus inhibitors as a paradigm for the chemotherapy of poxvirus infections. A1 - De Clercq,E, PY - 2001/4/9/pubmed PY - 2001/8/3/medline PY - 2001/4/9/entrez SP - 382 EP - 97 JF - Clinical microbiology reviews JO - Clin. Microbiol. Rev. VL - 14 IS - 2 N2 - Poxviruses continue to pose a major threat to human health. Monkeypox is endemic in central Africa, and the discontinuation of the vaccination (with vaccinia virus) has rendered most humans vulnerable to variola virus, the etiologic agent of smallpox, should this virus be used in biological warfare or terrorism. However, a large variety of compounds have been described that are potent inhibitors of vaccinia virus replication and could be expected to be active against other poxviruses as well. These compounds could be grouped in different classes: (i) IMP dehydrogenase inhibitors (e.g., EICAR); (ii) SAH hydrolase inhibitors (e.g., 5'-noraristeromycin, 3-deazaneplanocin A, and various neplanocin A derivatives); (iii) OMP decarboxylase inhibitors (e.g., pyrazofurin) and CTP synthetase inhibitors (e.g., cyclopentenyl cytosine); (iv) thymidylate synthase inhibitors (e.g., 5-substituted 2'-deoxyuridines); (v) nucleoside analogues that are targeted at viral DNA synthesis (e.g., Ara-A); (vi) acyclic nucleoside phosphonates [e.g., (S)-HPMPA and (S)-HPMPC (cidofovir)]; and (vii) polyanionic substances (e.g., polyacrylic acid). All these compounds could be considered potential candidate drugs for the therapy and prophylaxis of poxvirus infections at large. Some of these compounds, in particular polyacrylic acid and cidofovir, were found to generate, on single-dose administration, a long-lasting protective efficacy against vaccinia virus infection in vivo. Cidofovir, which has been approved for the treatment of cytomegalovirus retinitis in immunocompromised patients, was also found to protect mice, again when given as a single dose, against a lethal aerosolized or intranasal cowpox virus challenge. In a biological warfare scenario, it would be advantageous to be able to use a single treatment for an individual exposed to an aerosolized poxvirus. Cidofovir thus holds great promise for treating human smallpox, monkeypox, and other poxvirus infections. Anecdotal experience points to the efficacy of cidofovir in the treatment of the poxvirus infections molluscum contagiosum and orf (ecthyma contagiosum) in immunosuppressed patients. SN - 0893-8512 UR - https://www.unboundmedicine.com/medline/citation/11292644/Vaccinia_virus_inhibitors_as_a_paradigm_for_the_chemotherapy_of_poxvirus_infections_ L2 - http://cmr.asm.org/cgi/pmidlookup?view=long&pmid=11292644 DB - PRIME DP - Unbound Medicine ER -