Antiviral therapeutics for viral infections of the central nervous system
Avindra Nath, Joseph R. Berger in Clinical Neurovirology, 2020
Therapy of viral infections of the central nervous system (CNS) introduces unique challenges in the management of critically ill patients. Most importantly, adequate concentrations of active metabolite must be delivered to the site of infection; thus, lipophilicity is an essential drug characteristic for the treatment of encephalitis, one that does not exist for most medications employed in the treatment of CNS disease. Failure to achieve adequate concentrations of drug at the site of disease potentially can lead to a poor neurologic outcome as well as the potential for the development of antiviral resistance. In spite of these hurdles, success has been achieved in the treatment of a few viral infections of the brain. Arguably, the most significant successes have achieved with compliant highly active antiviral therapy for Human Immunodeficiency Virus infection and herpes simplex virus infections [1].
Sexually Transmitted Diseases
Peter Sagar, Andrew G. Hill, Charles H. Knowles, Stefan Post, Willem A. Bemelman, Patricia L. Roberts, Susan Galandiuk, John R.T. Monson, Michael R.B. Keighley, Norman S. Williams in Keighley & Williams’ Surgery of the Anus, Rectum and Colon, 2019
Patients with STIs often present with non-specific symptoms and findings. With STIs that involve the anal canal, patients frequently report a significant amount of pain. It is hypothesised that this pain is due to the extensive sensory nerves innervating the anal canal. Because of the pain, which in turn leads to reflex spasm of the anal sphincter, patients will often report constipation and tenesmus. Infections that spare the anal canal are usually associated with mucopurulent or bloody discharge. Clinical evaluation of the anus and rectum is necessary. However, clinical evaluation alone is not sensitive enough and must be performed in conjunction with other diagnostic tests. In the United States most young, sexually active patients who have genital, anal or perianal ulcers have either genital herpes or syphilis; however, more than one aetiological agent can be present. Specific evaluation of genital, anal or perianal ulcers includes: 1) syphilis serology, darkfield examination (dark ground illumination), or polymerase chain reaction (PCR) testing if available; 2) culture or PCR testing for genital herpes and 3) serologic testing for type-specific herpes simplex virus (HSV) antibody.2 Ulcers that have an unusual appearance or are unresponsive to initial therapy should be biopsied to help identify their aetiology. HIV testing should be performed on all persons with genital, anal or perianal ulcers with indeterminate HIV status.7 The practitioner should also have knowledge of disease incidence within the community in question.
Endometrial inflammation
T. Yee Khong, Annie N. Y. Cheung, Wenxin Zheng, Richard Wing-Cheuk Wong, Hao Chen in Diagnostic Endometrial Pathology, 2019
There are few documented cases of herpes simplex endometritis. Reported cases have occurred as a component of fatal herpes simplex viremia, in conjunction with herpes simplex cervicitis and in endometrial specimens from women with miscarriages in whom there was no clinical suspicion of herpes simplex infection. On microscopic examination, herpes simplex endometritis is characterised by the finding of multinucleated epithelial and stromal cells with enlarged, ground-glass nuclei containing eosinophilic intranuclear inclusions. There may be focal necrosis of endometrium associated with acute inflammation.20 The diagnosis can be confirmed by demonstration of stromal and epithelial cells showing immunoreactivity to herpes simplex virus antigens.
Integrating network pharmacology and experimental validation to decipher the mechanism of the Chinese herbal prescription JieZe-1 in protecting against HSV-2 infection
Published in Pharmaceutical Biology, 2022
Tong Liu, Qingqing Shao, Wenjia Wang, Yonggui Ma, Tianli Liu, Ximing Jin, Jianguo Fang, Guangying Huang, Zhuo Chen
HSV-2 (Herpes simplex virus type 2) is a sexually transmitted virus that causes genital herpes. At present, infection with HSV-2 is lifelong and incurable. An estimated 491 million (13%) people aged 15–49 years worldwide were living with the infection in 2016 (World Health Organization 2020). Women are more susceptible to HSV-2 infection than men, with the infection rate highest among women of childbearing age (James and Kimberlin 2015). Upon infection early in the pregnancy, the virus can be transmitted through the placenta, causing foetal abortion, neonatal malformation, and permanent neurological damage, which seriously affect the quality of the birth population (Johnston and Wald 2016). Genital herpes (GH) caused by HSV-2 is a global issue. Currently, nucleoside antiviral drugs are mainly used to treat HSV-2 infection. New therapeutic drugs and effective vaccines have not been found.
Immunotoxins and nanobody-based immunotoxins: review and update
Published in Journal of Drug Targeting, 2021
Mohammad Reza Khirehgesh, Jafar Sharifi, Fatemeh Safari, Bahman Akbari
Herpes simplex virus serotype2 (HSV-2) is one of the most common sexually transmitted infections (STIs) that causes genital herpes disease. HSV-2 glycoprotein D (gD2) is an antigen essential for virus entry into cells and cell-to-cell spread. Therefore, targeting of HSV-2 infected cells by anti-gD2 IT may lead to blocking virus cell-to-cell transmission. After immunisation of a llama with recombinant gD2, an anti-gD2 Nb (R33) was generated. The affinity of R33 to gD2-positive cell line (Z4/6) was confirmed with flow cytometry assays. Because of the ability of the R33 Nb to neutralise the virus-infected cells, R33ExoA IT was produced. The recombinant R33ExoA expressed and cytotoxic activity in HSV-2 infected cells line confirmed in vitro date shown nanomolar range [162].
Signal peptide peptidase: a potential therapeutic target for parasitic and viral infections
Published in Expert Opinion on Therapeutic Targets, 2022
Christopher Schwake, Michael Hyon, Athar H. Chishti
The human herpes simplex virus types −1 and −2 (HSV-1/2) cause chronic lifelong infection that are mainly asymptomatic; however, blisters and sores can occur in infected individuals. Furthermore, HSV-1 can cause serious eye infections with risk of blindness. HSV-1 utilizes its envelope protein glycoprotein K (gK) for binding to SPP during infection and this interaction is required for replication (Figure 5D) [78]. No other HSV-1 gene binds to SPP except gK. A later study investigating the involvement of SPP in HSV-1 infection in vivo using an inducible SPP mouse knockout model confirmed gK as a binding partner of SPP [79]. Interestingly, they found that viral latency was also reduced in SPP knockout mice [79]. Pharmacological inhibition of SPP with five small molecule inhibitors including (Z-LL)2-ketone and L685,485 were able to reduce HSV-1 replication in tissue culture [80]. Viral replication was impacted due to HSV-1 gene expression being blocked in the nucleus but not in the cytoplasm in the presence of SPP inhibitors [80]. Importantly, (Z-LL)2-ketone administered to the eyes of mice infected with HSV-1 significantly decreased viral replication. Therefore, disruption of SPP activity may be a potential therapy for HSV-1 induced eye disease, and should be examined further, especially due to concern of acyclovir-resistant isolates and the lack of a prophylactic vaccine [81].
Related Knowledge Centers
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