Introduction
In recent years, herpes virus infection has become a global concern due
to its significant threat to public health. Herpesvirus is an infectious
agent belonging to the herpesviridae family, which can cause latent and
lytic infections in humans and various animals [1]. According to its
genome organization and sequence, herpes viruses are subdivided into
three subfamilies, namely α Herpesvirus, β Herpesvirus and Herpesvirus C
[2]. There are currently eight known types of herpes viruses that
can infect humans, known as human herpesvirus HHV, including herpes
simplex virus (HSV-1 and HSV-2), varicella zoster virus (VZV), EB virus,
human herpesvirus 6 (variants A and B), human herpesvirus 7, Kaposi
sarcoma associated herpesvirus, and human cytomegalovirus (CMV) [3,
4]. The main feature of this virus family is its opposition to
replication within the host cell and is not completely eliminated,
leading to latent infection [2]. During the incubation period, the
expression of viral protein is restricted, which limits the detection of
the host immune system [5, 6]. According to the World Health
Organization, there are currently 3.7 billion people under the age of 50
infected with herpes simplex virus type 1 and 491 million people aged 15
to 49 infected with herpes simplex virus type 2 worldwide.
Acyclovir (ACV) is an antiviral drug of guanine nucleoside analogues and
is highly selective α Herpesvirus inhibitors [7] [8], due to
their high selectivity and low cytotoxicity, are considered the
beginning of a new era of antiviral therapy [9, 10]. Discovered in
the early 1970s, it entered clinical research in 1977 and was first
approved as an antiviral drug in 1982[7, 11, 12]. Subsequently, many
potential anti herpesvirus compounds were synthesized, and currently,
many have been approved and marketed [13-15]. They include GCV and
derivatives (prodrugs) of these drugs, VACV and FCV [11, 16, 17].
These are nucleoside analogues, which are highly selective inhibitors of
virus encoded DNA polymerase (DNA pol). Its antiviral effect is due to
the inhibition of viral DNA synthesis in the mechanism of competitive
incorporation of deoxyguanosine triphosphate (dGTP) into the DNA chain
[18], thereby reducing symptoms, virus excretion and outbreak
frequency, which can be used as inhibitory treatment, prophylactic
treatment and risk adaptive prevention. These studies provide more novel
structures for the development of ACV like antiviral drugs, which can
more effectively address the shortcomings of ACV and improve antiviral
ability, bringing a more open perspective for disease treatment [10]
[19].
So far, there has been no targeting of people β Specific, efficient, and
safe antiviral drugs for herpes virus and human herpesvirus C [17].
Currently, registered anti herpesvirus drugs can only control infections
caused by HSV, VZV, and CMV [17] [20]. ACV is a first-line
treatment drug for HSV-1, HSV-2, and VZV. ACV and VACV can be used as
inhibitory treatments to prevent oral and genital recurrence of diseases
caused by HSV-1 and HSV-2 [15, 16]. GCV inhibits replication of
herpes A virus, CMV, EB virus, HHV6, 7, and 8, as well as hepatitis B
virus (HBV). In clinical practice, it is the preferred drug for treating
cytomegalovirus infections [21-23]. With the widespread use of the
”lovir” family of drugs, drug related ADEs have also received attention.
Unfortunately, little is known about the differences in the real world
of the ”lovir” family of drugs, and there are still many doubts about
their medication choices, apart from focusing on therapeutic effects.
FAERS is a spontaneous reporting system for post market drug adverse
events in the United States. It has a large amount of data, diverse data
information, and is open to the public for free, including adverse
events and medication errors submitted to the FDA [24]. The
information reported in this database is aimed at supporting the FDA’s
post market safety monitoring program for drugs and therapeutic
biological products. Therefore, it can be used to identify new drug
related adverse events that were not previously observed in clinical
trials. Currently, both domestically and internationally, adverse event
signal mining methods based on FAERS big data are widely used, which can
fully utilize a large amount of real-world ADEs data, monitor drug
safety information after marketing, and timely discover new and serious
ADEs.
To rationalize the selection of anti-herpes virus drugs in the real
world, this article is based on the FAERS database and conducts signal
mining on the ADEs of DNA polymerase inhibitor class anti herpetic
drugs. Based on the discovery and summary of DNA polymerase inhibitor
class anti herpetic drugs ADEs, it aims to analyze their causes in the
real world, propose reasonable medication recommendations, refine their
usage rules, and develop necessary alternative strategies, To provide
protection against herpes virus infection and provide guidance and
reference for the rational and individualized use of clinical drugs.