Abstract
Recently, the problem of viral infection, particularly the infection with herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2), has dramatically increased and caused a significant challenge to public health due to the rising problem of drug resistance. The antiherpetic drug resistance crisis has been attributed to the overuse of these medications, as well as the lack of new drug development by the pharmaceutical industry due to reduced economic inducements and challenging regulatory requirements. Therefore, the development of novel antiviral drugs against HSV infections would be a step forward in improving global combat against these infections. The incorporation of biologically active natural products into anti-HSV drug development at the clinical level has gained limited attention to date. Thus, the search for new drugs from natural products that could enter clinical practice with lessened resistance, less undesirable effects, and various mechanisms of action is greatly needed to break the barriers to novel antiherpetic drug development, which, in turn, will pave the road towards the efficient and safe treatment of HSV infections. In this review, we aim to provide an up-to-date overview of the recent advances in natural antiherpetic agents. Additionally, this paper covers a large scale of phenolic compounds, alkaloids, terpenoids, polysaccharides, peptides, and other miscellaneous compounds derived from various sources of natural origin (plants, marine organisms, microbial sources, lichen species, insects, and mushrooms) with promising activities against HSV infections; these are in vitro and in vivo studies. This work also highlights bioactive natural products that could be used as templates for the further development of anti-HSV drugs at both animal and clinical levels, along with the potential mechanisms by which these compounds induce anti-HSV properties. Future insights into the development of these molecules as safe and effective natural anti-HSV drugs are also debated.
Highlights
Infection with herpes simplex virus (HSV) has been recognized since antiquity in humans, the first in vitro cultivation of HSV was assayed in 1925 [1]
herpes simplex virus type 1 (HSV-1) is generally associated with oral or facial infection and encephalitis, while herpes simplex virus type 2 (HSV-2) is accountable for genital herpes, which is an important sexually transmitted disease [5]
We have to mention that there is a relative lack of information concerning in vivo testing of compounds assayed in the Vero cell model system against HSV, as described, for example, here [119]
Summary
Infection with herpes simplex virus (HSV) has been recognized since antiquity in humans, the first in vitro cultivation of HSV was assayed in 1925 [1]. (HSV-1) and herpes simplex virus type 2 (HSV-2) have been distinguished from each other by different clinical manifestations and tropism [2]. HSV belongs to Herpesviridae, which is a broad family of enveloped-DNA viruses that induce numerous clinically substantial syndromes in both adults and neonates. Several factors including viral entrance, the nature of the disease, and degree of host immune competency could affect the induced syndromes [3,4]. HSV-1 is generally associated with oral or facial infection and encephalitis, while HSV-2 is accountable for genital herpes, which is an important sexually transmitted disease [5]. Infection with HSV-2 can cause recurrent, painful genital lesions and is often connected with negative psychosocial consequences such as shame, anxiety, and depression
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