Selective Inhibition of Vaccinia Virus by the Antibiotic Rifampicin

Heller, E. D.; Argaman, M.; Levy, Haim; Goldblum, Natan

doi:10.1038/222273a0

Cited by 96 publications

(27 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Controls included uninfected cells, which have a low fluorescence background (Fig. 2), and vvGFP-infected cells treated with either rifampin, an inhibitor of viral assembly (11,20), hydroxyurea, which blocks DNA replication (22), or AraC, an inhibitor of DNA synthesis in VV (12, 2). These control treatments display low levels of fluorescence regardless of whether they inhibit late or early in the replication cycle.…”

Section: Resultsmentioning

confidence: 99%

New Class of Orthopoxvirus Antiviral Drugs That Block Viral Maturation

Byrd¹,

Bolken

Mjalli³

et al. 2004

J Virol

View full text Add to dashboard Cite

By using a homology-based bioinformatics approach, a structural model of the vaccinia virus (VV) I7L proteinase was developed. A unique chemical library of ϳ51,000 compounds was computationally queried to identify potential active site inhibitors. The resulting biased subset of compounds was assayed for both toxicity and the ability to inhibit the growth of VV in tissue culture cells. A family of chemotypically related compounds was found which exhibits selective activity against orthopoxviruses, inhibiting VV with 50% inhibitory concentrations of 3 to 12 M. These compounds exhibited no significant cytotoxicity in the four cell lines tested and did not inhibit the growth of other organisms such as Saccharomyces cerevisiae, Pseudomonas aeruginosa, adenovirus, or encephalomyocarditis virus. Phenotypic analyses of virus-infected cells were conducted in the presence of active compounds to verify that the correct biochemical step (I7L-mediated core protein processing) was being inhibited. Electron microscopy of compound-treated VV-infected cells indicated a block in morphogenesis. Compound-resistant viruses were generated and resistance was mapped to the I7L open reading frame. Transient expression with the mutant I7L gene rescued the ability of wild-type virus to replicate in the presence of compound, indicating that this is the only gene necessary for resistance. This novel class of inhibitors has potential for development as an efficient antiviral drug against pathogenic orthopoxviruses, including smallpox.

show abstract

Section: Resultsmentioning

confidence: 99%

New Class of Orthopoxvirus Antiviral Drugs That Block Viral Maturation

Byrd¹,

Bolken

Mjalli³

et al. 2004

J Virol

View full text Add to dashboard Cite

show abstract

“…Rifampin was also initially studied as an antiviral (in particular the poxviruses, based on the viruses containing an RNA polymerase) and as an antifungal agent combined with amphotericin B in the early 1970s (27,116,175,212,235). The antiviral activity of rifampin did not progress from laboratory studies because the required rifampin dosage needed to achieve treatment levels would be toxic, while more effective antifungal agents with less toxicity were later developed that made the role of rifampin antifungal synergy redundant (27,116,175,212).…”

Section: Introductionmentioning

confidence: 99%

“…The antiviral activity of rifampin did not progress from laboratory studies because the required rifampin dosage needed to achieve treatment levels would be toxic, while more effective antifungal agents with less toxicity were later developed that made the role of rifampin antifungal synergy redundant (27,116,175,212).…”

Section: Introductionmentioning

confidence: 99%

Rifampin Combination Therapy for Nonmycobacterial Infections

2010

View full text Add to dashboard Cite

SUMMARY The increasing emergence of antimicrobial-resistant organisms, especially methicillin-resistant Staphylococcus aureus (MRSA), has resulted in the increased use of rifampin combination therapy. The data supporting rifampin combination therapy in nonmycobacterial infections are limited by a lack of significantly controlled clinical studies. Therefore, its current use is based upon in vitro or in vivo data or retrospective case series, all with major limitations. A prominent observation from this review is that rifampin combination therapy appears to have improved treatment outcomes in cases in which there is a low organism burden, such as biofilm infections, but is less effective when effective surgery to obtain source control is not performed. The clinical data support rifampin combination therapy for the treatment of prosthetic joint infections due to methicillin-sensitive S. aureus (MSSA) after extensive debridement and for the treatment of prosthetic heart valve infections due to coagulase-negative staphylococci. Importantly, rifampin-vancomycin combination therapy has not shown any benefit over vancomycin monotherapy against MRSA infections either clinically or experimentally. Rifampin combination therapy with daptomycin, fusidic acid, and linezolid needs further exploration for these severe MRSA infections. Lastly, an assessment of the risk-benefits is needed before the addition of rifampin to other antimicrobials is considered to avoid drug interactions or other drug toxicities.

show abstract

“…Their mode of action involves the bacterial RNA polymerase (1). After the discovery that these drugs could also inhibit the replication of certain viruses, particularly adenovirus and vaccinia (2)(3)(4), it became of interest to explore the extent and possibly determine the nature of this antiviral activity. Toward this end, we obtained some samples of these materials in April of 1970* whose structures are shown in Fig.…”

mentioning

confidence: 99%

Effect of Rifampicin and Two of Its Derivatives on Cells Infected With Moloney Sarcoma Virus

Calvin

Joss

Hackett

et al. 1971

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

It is shown that rifampicin, and especially the related antibiotic 2',6'-dimethyl-N(4')-benzyl-N(4')-[desmethylirifampicin (DMB-rifampicin) can inhibit focus formation by Moloney sarcoma virus on BALB/3T3 tissue cultures. At 10 ug/ml DMB-rifampicin totally inhibits focus formation while reducing virus replication by at least a factor of fifty and cell proliferation by only a factor of three. These observations, taken together with those of others, suggest a role for an RNA-dependent DNA polymerase and the gene for its synthesis both in normal cell processes and in the transformation process.

show abstract

Selective Inhibition of Vaccinia Virus by the Antibiotic Rifampicin

Cited by 96 publications

References 9 publications

New Class of Orthopoxvirus Antiviral Drugs That Block Viral Maturation

New Class of Orthopoxvirus Antiviral Drugs That Block Viral Maturation

Rifampin Combination Therapy for Nonmycobacterial Infections

Effect of Rifampicin and Two of Its Derivatives on Cells Infected With Moloney Sarcoma Virus

Contact Info

Product

Resources

About