ChemInform Abstract: Towards an Effective Chemotherapy of Virus Infections: Therapeutic Potential of Cidofovir [(S)-1-[3-Hydroxy-2-(phosphonomethoxy)propyl]cytosine, HPMPC] for the Treatment of DNA Virus Infections.

ChemInform ◽  
2010 ◽  
Vol 29 (36) ◽  
pp. no-no
Author(s):  
E. DE CLERCQ
Keyword(s):  
Therapeutic Potential ◽  
Virus Infections ◽  
Dna Virus

Towards an Effective Chemotherapy of Virus Infections: Therapeutic Potential of Cidofovir [(S)-1-[3-Hydroxy-2-(phosphonomethoxy)propyl]cytosine, HPMPC] for the Treatment of DNA Virus Infections

1998 ◽  
Vol 63 (4) ◽  
pp. 480-506 ◽  
Author(s):  
Erik De Clercq
Keyword(s):  
Antiviral Activity ◽  
Therapeutic Potential ◽  
Antiviral Agents ◽  
Human Herpesvirus ◽  
Antiviral Agent ◽  
Molluscum Contagiosum ◽  
Virus Infections ◽  
Laryngeal Papillomatosis ◽  
Dna Virus ◽  
Herpesvirus Type

The acyclic nucleoside phosphonate HPMPC [(S)-1-[3-hydroxy-2-(phosphonomethoxy)propyl]cytosine, cidofovir, Vistide®] has a unique profile among the antiviral agents in that it is active against a much broader spectrum of DNA viruses than any other antiviral agent, and, furthermore, shows a long-lasting antiviral activity, thus enabling infrequent dosing (for intravenous administration, as infrequent as once a week or every other week). HPMPC owes its antiviral activity to a selective inhibitory effect on viral DNA synthesis: as has been demonstrated for human cytomegalovirus (CMV), HPMPC leads to DNA chain termination following the incorporation of two consecutive HPMPC residues. The activity spectrum of HPMPC encompasses herpes-, adeno-, polyoma-, papilloma-, and poxviruses. It has been approved for the treatment of CMV retinitis in AIDS patients and has proved effective in the treatment of herpes simplex virus (HSV) infections (particularly those that are resistant to acyclovir), human papilloma virus (HPV) infections (e.g. anogenital warts and recurrent laryngeal papillomatosis) and poxvirus infections (e.g. molluscum contagiosum). It is now further explored for its therapeutic potential in the treatment of HSV, CMV and HPV infections, and various other DNA virus infections, including adenovirus infections (e.g. keratoconjunctivitis), polyomavirus infections such as PML (progressive multifocal leukoencephalopathy), poxvirus infections (e.g. molluscum contagiosum), Epstein-Barr virus (EBV)-associated infections, and human herpesvirus type 8 (HHV-8)-associated infections (e.g. Kaposi's sarcoma).

scholarly journals TRIM29 promotes DNA virus infections by inhibiting innate immune response

2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Junji Xing ◽  
Ao Zhang ◽  
Hua Zhang ◽  
Jin Wang ◽  
Xian Chang Li ◽  
...  
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
Innate Immune ◽  
Virus Infections ◽  
Dna Virus

scholarly journals Clinical Potential of the Acyclic Nucleoside Phosphonates Cidofovir, Adefovir, and Tenofovir in Treatment of DNA Virus and Retrovirus Infections

2003 ◽  
Vol 16 (4) ◽  
pp. 569-596 ◽  
Author(s):  
Erik De Clercq
Keyword(s):  
Hepatitis B ◽  
Tenofovir Disoproxil Fumarate ◽  
Adefovir Dipivoxil ◽  
Cowpox Virus ◽  
Virus Infections ◽  
Molluscum Contagiosum Virus ◽  
Dna Virus ◽  
Immunodeficiency Virus ◽  
Acyclic Nucleoside Phosphonates ◽  
Acyclic Nucleoside

SUMMARY The acyclic nucleoside phosphonates HPMPC (cidofovir), PMEA (adefovir), and PMPA (tenofovir) have proved to be effective in vitro (cell culture systems) and in vivo (animal models and clinical studies) against a wide variety of DNA virus and retrovirus infections: cidofovir against herpesvirus (herpes simplex virus types 1 and 2 varicella-zoster virus, cytomegalovirus [CMV], Epstein-Barr virus, and human herpesviruses 6, 7, and 8), polyomavirus, papillomavirus, adenovirus, and poxvirus (variola virus, cowpox virus, vaccinia virus, molluscum contagiosum virus, and orf virus) infections; adefovir against herpesvirus, hepadnavirus (human hepatitis B virus), and retrovirus (human immunodeficiency virus types 1 [HIV-1] and 2 [HIV-2], simian immunodeficiency virus, and feline immunodeficiency virus) infections; and tenofovir against both hepadnavirus and retrovirus infections. Cidofovir (Vistide) has been officially approved for the treatment of CMV retinitis in AIDS patients, tenofovir disoproxil fumarate (Viread) has been approved for the treatment of HIV infections (i.e., AIDS), and adefovir dipivoxil (Hepsera) has been approved for the treatment of chronic hepatitis B. Nephrotoxicity is the dose-limiting side effect for cidofovir (Vistide) when used intravenously (5 mg/kg); no toxic side effects have been described for adefovir dipivoxil and tenofovir disoproxil fumarate, at the approved doses (Hepsera at 10 mg orally daily and Viread at 300 mg orally daily).

Routine use of duplex real-time PCR assays including a commercial internal control for molecular diagnosis of opportunistic DNA virus infections

2012 ◽  
Vol 185 (1) ◽  
pp. 136-141 ◽  
Author(s):  
Sonia Burrel ◽  
Christelle Fovet ◽  
Christel Brunet ◽  
Lydia Ovaguimian ◽  
Nathalie Hamm ◽  
...  
Keyword(s):  
Real Time ◽  
Molecular Diagnosis ◽  
Internal Control ◽  
Real Time Pcr ◽  
Virus Infections ◽  
Dna Virus ◽  
Pcr Assays

scholarly journals Compounds with Therapeutic Potential against Novel Respiratory 2019 Coronavirus

2020 ◽  
Vol 64 (5) ◽  
Author(s):  
Miguel Angel Martinez
Keyword(s):  
Ebola Virus ◽  
Therapeutic Potential ◽  
High Morbidity ◽  
Virus Infections ◽  
Humanized Mouse Model ◽  
Proinflammatory Responses ◽  
Inflammatory State ◽  
Human Coronaviruses ◽  
Novel Coronavirus ◽  
Respiratory Coronavirus

ABSTRACT Currently, the expansion of the novel human respiratory coronavirus (known as SARS-CoV-2 [severe acute respiratory syndrome coronavirus 2], COVID-2019 [coronavirus disease 2019], or 2019-nCoV [2019 novel coronavirus]) has stressed the need for therapeutic alternatives to alleviate and stop this new epidemic. The previous epidemics of infections by high-morbidity human coronaviruses, such as SARS-CoV in 2003 and the Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012, prompted the characterization of compounds that could be potentially active against the currently emerging novel coronavirus, SARS-CoV-2. The most promising compound is remdesivir (GS-5734), a nucleotide analog prodrug currently in clinical trials for treating Ebola virus infections. Remdesivir inhibited the replication of SARS-CoV and MERS-CoV in tissue cultures, and it displayed efficacy in nonhuman animal models. In addition, a combination of the human immunodeficiency virus type 1 (HIV-1) protease inhibitors lopinavir/ritonavir and interferon beta (LPV/RTV–IFN-β) was shown to be effective in patients infected with SARS-CoV. LPV/RTV–IFN-β also improved clinical parameters in marmosets and mice infected with MERS-CoV. Remarkably, the therapeutic efficacy of remdesivir appeared to be superior to that of LPV/RTV–IFN-β against MERS-CoV in a transgenic humanized mouse model. The relatively high mortality rates associated with these three novel human coronavirus infections, SARS-CoV, MERS-CoV, and SARS-CoV-2, have suggested that proinflammatory responses might play a role in the pathogenesis. It remains unknown whether the generated inflammatory state should be targeted. Therapeutics that target the coronavirus alone might not be able to reverse highly pathogenic infections. This minireview aims to provide a summary of therapeutic compounds that have shown potential in fighting SARS-CoV-2 infections.

Effect of CMX001 on Levels of DNA Virus In Patients After Allogeneic Stem Cell Transplantation.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4550-4550
Author(s):  
Don A. Gabriel ◽  
Julia Whitley ◽  
Kamakshi Rao ◽  
Charles van der Horst ◽  
Jonathan Serody ◽  
...  
Keyword(s):  
Viral Infections ◽  
Conflicts Of Interest ◽  
Hemorrhagic Cystitis ◽  
Antiviral Drug ◽  
Clinical Problem ◽  
Marrow Transplant ◽  
Pericardial Fluid ◽  
Virus Infections ◽  
Dna Virus ◽  
Cycle Number

Abstract Abstract 4550 Latent viral infections occurring in the post bone marrow transplant period remain a significant clinical problem. New and effective antiviral drugs (AVD) are needed to provide adequate therapy for infected patients. We report the use of a new oral AVD, CMX001 (Chimerix Inc. Durham, NC) to treat DNA virus infections in six severely ill patients.Pt #123456Adeno Blood (PCR Cycles)Pre: 30.6Pre: 33.1Post: 37.3Post: NegBK polyoma virus Urine (log copies/mL)Pre: 4.89Pre: 4.86Pre: 6.54Pre: 9.06Post: 7.88Post: 5.99Post: 7.55Post: 7.16BKV BloodCleared after 1 dosePre: No valueCleared at 6 doses;Post: detectableHHV6 Blood (PCR Cycles)Pre: 42Post: 39.9Dose (mg/kg) biw22444 reduced to 32StatusDied GVHDDied GVHDDied GVHD + SepsisDied GVHDAliveAlive All patients had grade 2 or greater gut graft versus host disease (GVHD) during or after CMX001 treatment. The Table shows viral levels before and after treatment with CMX001 twice/wk. Pt 1's AV cycle number fluctuated and never cleared. A higher cycle number indicates less virus. Pt 2 cleared AV from blood after first dose, but urine, stool, gut biopsies remained AV positive. Pt 3's HHV6 plasma PCR levels fluctuated, but the pericardial fluid levels had cleared at autopsy. Pt 4 did not have pre dosing blood BKV PCR levels taken and his subsequent blood BKV low level was measurable (below the positive limit level). Interestingly, however, the patient's BKV related hemorrhagic cystitis (HC) symptoms resolved after 4 doses of CMX001. Pt 5's BKV HC symptoms also resolved after 4 doses of drug, and his positive blood viral level cleared after 6 doses. Pt 6 discontinued drug because of abdominal pain and the need for NPO, but his hemorrhagic cystitis symptoms had abated. No specific toxicities were documented in these severely ill patients with gut GVHD, but gut pain and transient thrombocytopenia were observed. In summary, one of 2 pts with AV cleared their blood. BKV was not cleared from urine, but 2/4 cleared BKV from blood. One patient with HHV6 did not clear blood DNA viral levels, but did clear pericardial fluid. In both cases of HC, symptoms resolved. Thus, CMX001 shows promise as new antiviral drug given its ability to decrease DNA viral levels in this small group of critically ill patients. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Antiviral therapy for human immunodeficiency virus infections.

1995 ◽  
Vol 8 (2) ◽  
pp. 200-239 ◽  
Author(s):  
E De Clercq
Keyword(s):  
Human Immunodeficiency Virus ◽  
Binding Site ◽  
Therapeutic Potential ◽  
Current Knowledge ◽  
Antisense Oligodeoxynucleotides ◽  
Virus Infections ◽  
Transcription Inhibitors ◽  
Fusion Inhibitors ◽  
Immunodeficiency Virus ◽  
Acyclic Nucleoside Phosphonates

Depending on the stage of their intervention with the viral replicative cycle, human immunodeficiency virus inhibitors could be divided into the following groups: (i) adsorption inhibitors (i.e., CD4 constructs, polysulfates, polysulfonates, polycarboxylates, and polyoxometalates), (ii) fusion inhibitors (i.e., plant lectins, succinylated or aconitylated albumins, and betulinic acid derivatives), (iii) uncoating inhibitors (i.e., bicyclams), (iv) reverse transcription inhibitors acting either competitively with the substrate binding site (i.e., dideoxynucleoside analogs and acyclic nucleoside phosphonates) or allosterically with a nonsubstrate binding site (i.e., non-nucleoside reverse transcriptase inhibitors), (v) integration inhibitors, (vi) DNA replication inhibitors, (vii) transcription inhibitors (i.e., antisense oligodeoxynucleotides and Tat antagonists), (viii) translation inhibitors (i.e., antisense oligodeoxynucleotides and ribozymes), (ix) maturation inhibitors (i.e., protease inhibitors, myristoylation inhibitors, and glycosylation inhibitors), and finally, (x) budding (assembly/release) inhibitors. Current knowledge, including the therapeutic potential, of these various inhibitors is discussed. In view of their potential clinical the utility, the problem of virus-drug resistance and possible strategies to circumvent this problem are also addressed.

Outcome of mixed DNA virus infections on Spodoptera exigua susceptibility to SeMNPV

2018 ◽  
Vol 92 (2) ◽  
pp. 885-893
Author(s):  
Laila Gasmi ◽  
Ada Frattini ◽  
Mylène Ogliastro ◽  
Salvador Herrero
Keyword(s):  
Spodoptera Exigua ◽  
Virus Infections ◽  
Dna Virus
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