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  1. Balakrishnan KN, Abdullah AA, Bala JA, Jesse FFA, Abdullah CAC, Noordin MM, et al.
    Infect Genet Evol, 2021 06;90:104783.
    PMID: 33640483 DOI: 10.1016/j.meegid.2021.104783
    OBJECTIVE: This study investigated the suitability of siRNA targeting specific genes that cause inhibition of virus replication in vitro especially for the virus that capable of crossing placenta and we employed a novel transplacental rat cytomegalovirus that mimics infection in human.

    METHODS: Six unique siRNAs with three each targeting different regions of IE2 (ie2a, ie2b and ie2c) and DNA polymerase (dpa, dpb and dpc) were prepared and tested for antiviral activities. The efficacy as an antiviral was determined in in-vitro by measuring TCID50 virus titer, severity of virus-induced cytopathic effect (CPE), intracellular viral genome loads by droplet digital PCR, the degree of apoptosis in siRNA-treated cells and relative expression of viral mRNA in infected Rat Embryo Fibroblast (REF) cells.

    FINDINGS: Remarkably, the siRNAs: dpa, dpb and IE2b, significantly reduced virus yield (approximately >90%) compared to control group at day 18 post infection (p.i). Changes in CPE indicated that DNA polymerase siRNAs were capable of protecting cells against CMV infection at day 14 p.i with higher efficiency than GCV (at the concentration of 300 pmol). Gene expression analysis revealed a marked down regulation of the targeted DNA polymerase gene (73.9%, 96.0% and 90.7% for dpa, dpb and dpc siRNA, respectively) and IE2 gene (50.8%, 49.9% and 15.8% for ie2a, ie2b and ie2c siRNA, respectively) when measured by RT-qPCR. Intracellular viral DNA loads showed a significant reduction for all the DNA polymerase siRNAs (dpa: 96%, dpb: 98% and dpc:92) compared to control group (P 

    Matched MeSH terms: Cytomegalovirus Infections/drug therapy
  2. A Abdullah A, Abdullah R, A Nazariah Z, N Balakrishnan K, Firdaus J Abdullah F, A Bala J, et al.
    Antivir Chem Chemother, 2018;26:2040206618811413.
    PMID: 30449131 DOI: 10.1177/2040206618811413
    BACKGROUND: Viruses are obligate parasites that depend on the cellular machinery of the host to regenerate and manufacture their proteins. Most antiviral drugs on the market today target viral proteins. However, the more recent strategies involve targeting the host cell proteins or pathways that mediate viral replication. This new approach would be effective for most viruses while minimizing drug resistance and toxicity.

    METHODS: Cytomegalovirus replication, latency, and immune response are mediated by the intermediate early protein 2, the main protein that determines the effectiveness of drugs in cytomegalovirus inhibition. This review explains how intermediate early protein 2 can modify the action of cyclosporin A, an immunosuppressive, and antiviral drug. It also links all the pathways mediated by cyclosporin A, cytomegalovirus replication, and its encoded proteins.

    RESULTS: Intermediate early protein 2 can influence the cellular cyclophilin A pathway, affecting cyclosporin A as a mediator of viral replication or anti-cytomegalovirus drug.

    CONCLUSION: Cyclosporin A has a dual function in cytomegalovirus pathogenesis. It has the immunosuppressive effect that establishes virus replication through the inhibition of T-cell function. It also has an anti-cytomegalovirus effect mediated by intermediate early protein 2. Both of these functions involve cyclophilin A pathway.

    Matched MeSH terms: Cytomegalovirus Infections/drug therapy*
  3. Tajunisah I, Reddy SC, Tan LH
    Int Ophthalmol, 2009 Apr;29(2):85-90.
    PMID: 18026692
    A rare case of acute retinal necrosis caused by cytomegalovirus in an immunocompetent adult, diagnosed by polymerase chain reaction of vitreous aspirate, with good visual outcome after intravitreal and intravenous ganciclovir and oral prednisolone therapy, is reported. A 50-year-old healthy lady presented with redness and diminution of vision in her right eye of 10 days duration. She had anterior chamber inflammation, marked vitritis, and anterior retinal necrosis in the right eye. Blood and other investigations did not reveal any infectious diseases and HIV testing was negative. The retinal lesions and panuveitis resolved with treatment. Two months later she developed retinal detachment which was treated successfully. The best-corrected vision was 6/12 in the right eye. Seven cases of cytomegalovirus ocular infection in immunocompetent healthy adults, reported in the literature, were reviewed. The different presentations of this disease and the importance of suspecting this causative agent are highlighted.
    Matched MeSH terms: Cytomegalovirus Infections/drug therapy
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