{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T20:58:36Z","timestamp":1793221116686,"version":"4.5.0"},"reference-count":36,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2003,7,1]],"date-time":"2003-07-01T00:00:00Z","timestamp":1057017600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2003,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            In the event of a bioterrorism attack using smallpox virus, there currently is no approved drug for the treatment of infections with this virus. We have reported previously that (\n            <jats:italic>S<\/jats:italic>\n            )-1-[3-hydroxy-2-(phosphonomethoxy)propyl]cytosine (HPMPC) (also known as cidofovir [CDV]) has good activity against poxvirus infections; however, a major limitation is the requirement for intravenous administration. Two related acyclic nucleoside phosphonates (ANPs), adefovir (PMEA) and tenofovir (PMPA), are active against human immunodeficiency virus or hepatitis B virus but do not have activity against the orthopoxviruses. Therefore, we have evaluated a number of analogs and potential oral prodrugs of these three compounds for their ability to inhibit the replication of vaccinia virus or cowpox virus in tissue culture cells. The most-active compounds within the CDV series were (\n            <jats:italic>S<\/jats:italic>\n            )-HPMPA and (butyl\n            <jats:sc>l<\/jats:sc>\n            -alaninyl) cyclic HPMPC, with 50% effective concentrations (EC\n            <jats:sub>50<\/jats:sub>\n            s) from 4 to 8 \u03bcM, compared with 33 to 43 \u03bcM for CDV. Although PMEA itself was not active, adefovir dipivoxil {bis[(pivaloyl)oxymethyl] PMEA} and bis(butyl\n            <jats:sc>l<\/jats:sc>\n            -alaninyl) PMEA were active against both viruses, and bis(butyl\n            <jats:sc>l<\/jats:sc>\n            -alaninyl) PME-N6-(cyclopropyl)DAP and (isopropyl\n            <jats:sc>l<\/jats:sc>\n            -alaninyl)phenyl PME-N6-(cyclopropyl)DAP were the most active compounds tested, with EC\n            <jats:sub>50<\/jats:sub>\n            s of 0.1 to 2.6 \u03bcM. In the PMPA series, none of the analogs tested had significantly better activity than PMPA itself. These data indicate that a number of these ANP derivatives have activity against vaccinia virus and cowpox virus in vitro and should be evaluated for their efficacies in animal models.\n          <\/jats:p>","DOI":"10.1128\/aac.47.7.2193-2198.2003","type":"journal-article","created":{"date-parts":[[2003,6,23]],"date-time":"2003-06-23T19:17:06Z","timestamp":1056395826000},"page":"2193-2198","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":59,"title":["Evaluation of Nucleoside Phosphonates and Their Analogs and Prodrugs for Inhibition of Orthopoxvirus Replication"],"prefix":"10.1128","volume":"47","author":[{"given":"Kathy A.","family":"Keith","sequence":"first","affiliation":[{"name":"University of Alabama School of Medicine, Birmingham, Alabama"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J. 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