1. Introduction
While millions of deaths were reported worldwide due to the SARS-CoV-2 pandemic [1], a new zoonotic disease, monkeypox (mPox), caused by the monkeypox virus (MPV), has become a severe public health concern. The monkeypox virus, closely related to the variola virus that causes smallpox, was initially identified in monkeys in 1958 [2] and in humans in a forested area of central Africa in 1970 [3, 4]. While mPox is endemic in parts of west and central Africa, its recent occurrence in a number of nonendemic locations outside of Africa has caused public health officials to express grave concerns [5]. Since smallpox was eradicated due to widespread vaccination, there have been very few natural outbreaks of the Orthopoxvirus until recently [2]. However, after the confirmed outbreaks in over 70 countries where the virus has not been reported before, the World Health Organization on July 23 issued its highest level alert, designating mPox as a public health emergency of international concern.
The MPV belongs to the genus Orthopoxvirus and in the family Poxviridae [2]. Currently, two variants of mPox in human are widely known. The Central African or Congo Basin variant (clade I) of mPox, which has a fatality rate of up to 10%, is the more severe of the two forms of mPox that affect humans [6]. In contrast, the West African variant (clade II), responsible for the current outbreak, causes a less severe disease with a lower mortality rate of 3% or less [4, 7]. The mPox can be transmitted among the community through a number of methods. The nosocomial and home routes of mPox transmission between people are extensively known, while sexual contact has also been proposed as a potential means of transmission [8, 9]. The disease can spread from one person to another if they are in close proximity to an infected individual’s skin sores, contaminated bedding, or big respiratory droplets [10]. Aside from the complications like pneumonitis, encephalitis, sight-threatening keratitis, and secondary bacterial infections, the typical clinical syndrome of mPox includes fever, rash, lymphadenopathy, and other symptoms [8]. The prominent-risk individuals of mPox sickness are immunocompromised individuals, younger people, elderly people, pregnant women, and people with diabetes and HIV/AIDS [5, 11].
Previously, smallpox vaccine Dryvax was most commonly used to treat both smallpox and mPox [12, 13]. Since late 2019, the COVID-19 pandemic has had a tremendous impact on the entire world, unequivocally highlighting the necessity of prophylactic measures in the early phases for the emerging viruses like MPV. Developing a vaccine capable of eliciting a sufficient immune response, effectively combating virus colonization and proliferation in the host, and eradicating the virus that has been introduced into the host can be a practical preventative approach to combat mPox virus-associated illness in the early stages. The MPV possesses a number of virulence factors which may help the virus to propagate within the host cell and circumvent the immune defenses. Shantier et al. reported that the cell surface binding protein of mPox plays a role in the pathogenesis of the virus [13]. The MPV virion membranes contain the cell surface binding protein E8L, which plays a crucial role in the attachment to the host cells [14]. This MPV protein attaches to chondroitin sulfate on the cell surface to enable virion attachment to the target cell [15]. Yousaf et al. also reported that it is produced in the outer membrane of the virus and helps in virion attachment to the target cell by binding to chondroitin sulfate on the cell surface [16]. As a result, the cell surface binding protein may be a promising vaccine target in order to create a unique and safe vaccination capable of triggering the desired immunological response. In order to understand disease etiology, monitor the immune system, develop a diagnostic assay, and design a vaccine, it is crucial to recognize epitopes in antigens [17]. During the recent outbreak of SARS-CoV-2, a number of vaccine candidates were proposed based on the identification of B cell and T cell epitopes. In an experiment by Singh et al., for example, they implemented immunoinformatics to develop a vaccine against the spike surface glycoprotein of SARS-CoV-2 using epitope-based peptide vaccines with high confidence [18]. Similar to the ebola virus, which is an antisense-strand RNA lethal virus that caused an epidemic, Dash et al. proposed an epitope-based vaccination against the virus’s glycoprotein [19]. In addition, a potential vaccine against the dengue virus, which poses a global health threat, was developed by Fadaka et al. using suitable adjuvants and linkers in addition to the selected epitopes [20].
This study is aimed at identifying the B and T cell epitopes on the cell surface binding protein and at designing an epitope-based peptide vaccine against the MPV by utilizing several computational databases and bioinformatics tools and software. Besides, this study is aimed at investigating the evolutionary relationship of this virulence protein with other similar types of proteins, as well as predict the protein’s three-dimensional structure and its refinement and quality assessment. Molecular docking analysis and molecular dynamic simulation were further employed in this study to investigate the interactions between the vaccine and host cell receptor as well as its stability. The outcome of this research will therefore enhance our knowledge to investigate potential therapeutics for emerging and reemerging pathogens and will serve as a basis for further in silico studies and benefit to the researchers.
