Evaluation of Topoisomerase Inhibitors as Potential Antiviral Agents

Maschera, Barbara; Ferrazzí, Eros; Rassu, Mario; Toni, M.; Palù, Giorgio

doi:10.1177/095632029300400202

Cited by 5 publications

(4 citation statements)

References 20 publications

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“…Several reports showed antiviral activities of DNA topoisomerase inhibitors. The anti-eukaryotic topoisomerase drugs camptothecin and etoposide were reported to interfere with the replication of simian virus 40 (Maschera et al, 1993). Podophyllotoxin derivatives such as etoposide (VP-16) and teniposide (VM-26) are known to be potent inhibitors of DNA topoisomerase II.…”

Section: Discussionmentioning

confidence: 99%

Inhibitory Effects of Podophyllotoxin Derivatives on Herpes Simplex Virus Replication

Sudo

Konno²,

Shigeta

et al. 1998

Antivir Chem Chemother

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Podophyllotoxin and its derivatives were examined for inhibitory effects on the replication of herpes simplex virus types 1 and 2 (HSV-1 and HSV-2), including acyclovir-resistant virus and clinical isolates. Deoxypodophyllotoxin (RD4-6266) proved to be a highly potent and selective inhibitor of all HSV strains in MRC-5 cells. EC50 values of RD4-6283 (in which the methylenedioxy ring A is modified) for HSV-1 and -2 were inferior to those of deoxypodophyllotoxin. However, podorhizol (RD4-6277) and 5'-methoxy-podorhizol (RD4-6276), in which ring C is absent, did not inhibit HSV replication. Moreover, RD4-6266 also inhibited the production of infectious virus particles of HSV-1 KOS strain and HSV-2 G strain. In contrast, none of the podophyllotoxin derivatives were found to have an antiviral effect against influenza A virus, respiratory syncytial virus or human cytomegalovirus in doses not toxic to the cells.

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Section: Discussionmentioning

confidence: 99%

Inhibitory Effects of Podophyllotoxin Derivatives on Herpes Simplex Virus Replication

Sudo

Konno²,

Shigeta

et al. 1998

Antivir Chem Chemother

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“…However, their use as anti-virals is far scarcer. Some studies have been performed in order to assess their potential as inhibitors of infection by several types of viruses, such as simian virus 40 [ 103 ], Kaposi’s sarcoma-associated herpesvirus [ 104 ] and HIV [ 105 ]. However, most of these studies have found that the drugs tested are either ineffective in inhibiting viral replication, or that they do so while simultaneously causing high cytotoxicity, thereby hindering their clinical use.…”

Section: Controlling Asf Through Inhibition Of the Viral Type II Tmentioning

confidence: 99%

The African Swine Fever Virus (ASFV) Topoisomerase II as a Target for Viral Prevention and Control

Coelho

Leitão

2020

Vaccines

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African swine fever (ASF) is, once more, spreading throughout the world. After its recent reintroduction in Georgia, it quickly reached many neighboring countries in Eastern Europe. It was also detected in Asia, infecting China, the world’s biggest pig producer, and spreading to many of the surrounding countries. Without any vaccine or effective treatment currently available, new strategies for the control of the disease are mandatory. Its etiological agent, the African swine fever virus (ASFV), has been shown to code for a type II DNA topoisomerase. These are enzymes capable of modulating the topology of DNA molecules, known to be essential in unicellular and multicellular organisms, and constitute targets in antibacterial and anti-cancer treatments. In this review, we summarize most of what is known about this viral enzyme, pP1192R, and discuss about its possible role(s) during infection. Given the essential role of type II topoisomerases in cells, the data so far suggest that pP1192R is likely to be equally essential for the virus and thus a promising target for the elaboration of a replication-defective virus, which could provide the basis for an effective vaccine. Furthermore, the use of inhibitors could be considered to control the spread of the infection during outbreaks and therefore limit the spreading of the disease.

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“…1 also inhibits replication of this virus, and deletion of Top1 is able to rescue virus infectivity from inhibition by 1 . Camptothecin has similar antiviral effects on simian virus 40, parvoviruses, adenoviruses, herpesviruses, and other DNA viruses; these studies (most from the 1990s) are summarized in the excellent review by Pantazis …”

Section: Uses Beyond Cancermentioning

confidence: 99%

“…1 also inhibits replication of this virus, and deletion of Top1 is able to rescue virus infectivity from inhibition by 1. 388 Camptothecin has similar antiviral effects on simian virus 40, 389 More recently, Takahashi et al 391 found that host Top1 interacts with the RNA-dependent RNA polymerase of Ebola virus (by coimmuoprecipitation) and aids in virus replication, and that Top1 knockdown reduces viral polymerase activity and Ebola replication. Camptothecin's role in preventing HIV infection and transmission has also been documented.…”

Section: Antiviral Activitymentioning

confidence: 99%

Topoisomerase 1B poisons: Over a half‐century of drug leads, clinical candidates, and serendipitous discoveries

Cinelli

2018

Medicinal Research Reviews

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Topoisomerases are DNA processing enzymes that relieve supercoiling (torsional strain) in DNA, are necessary for normal cellular division, and act by nicking (and then religating) DNA strands. Type 1B topoisomerase (Top1) is overexpressed in certain tumors, and the enzyme has been extensively investigated as a target for cancer chemotherapy. Various chemical agents can act as “poisons” of the enzyme’s religation step, leading to Top1‐DNA lesions, DNA breakage, and eventual cellular death. In this review, agents that poison Top1 (and have thus been investigated for their anticancer properties) are surveyed, including natural products (such as camptothecins and indolocarbazoles), semisynthetic camptothecin and luotonin derivatives, and synthetic compounds (such as benzonaphthyridines, aromathecins, and indenoisoquinolines), as well as targeted therapies and conjugates. Top1 has also been investigated as a therapeutic target in certain viral and parasitic infections, as well as autoimmune, inflammatory, and neurological disorders, and a summary of literature describing alternative indications is also provided. This review should provide both a reference for the medicinal chemist and potentially offer clues to aid in the development of new Top1 poisons.

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Evaluation of Topoisomerase Inhibitors as Potential Antiviral Agents

Cited by 5 publications

References 20 publications

Inhibitory Effects of Podophyllotoxin Derivatives on Herpes Simplex Virus Replication

Inhibitory Effects of Podophyllotoxin Derivatives on Herpes Simplex Virus Replication

The African Swine Fever Virus (ASFV) Topoisomerase II as a Target for Viral Prevention and Control

Topoisomerase 1B poisons: Over a half‐century of drug leads, clinical candidates, and serendipitous discoveries

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