**1. Introduction**

Ebola virus disease or EVD is a frequently fatal disease caused by a member of the *Filoviridae* family known as Ebola virus (EBOV) [1]. The pathogen was initially discovered in Africa in 1976 and then leaded to two serious outbreaks including the 2013–2016 outbreak of EVD in Western Africa that infected 28,652 people with

11,323 documented deaths; and 2018–2020 outbreak of EVD in the Democratic Republic of the Congo that affected 3481 people with 2299 documented deaths [2]. Ebola virus is transmitted to people from wild animals and spreads out in the mankind population by way of human-to-human transmission. The potential reservoirs of EBOV RNA are three species of African fruit bats [3]. The genome of this virus contains a negative-strand RNA that encodes six structural and one non-structural proteins, which can be employed as potential drug targets, including transmembrane glycoprotein (GP), nucleoprotein (NP), four viral protein (VP24, VP30, VP35, and VP40) and RNA polymerase (L) [4–6]. EBOV immediately suppresses the host's innate immune response and causes a severe febrile illness along with intense weakness, muscle pain, hypotension, coagulation disorders, sore throat, diarrhea, and vomiting [7–9].

Drug discovery and development for prevention of EBOV infections can be strikingly problematic due to the essential requirement of bio-safety level four (BSL-4) facilities that are needed for carrying out preclinical studies of Ebola virus [10, 11]. To date, there is only one approved vaccine for prevention of Ebola virus disease [12] and several recent FDA approved monoclonal antibody treatments for the patients [13–15]. The traditional drug discovery process remains timeconsuming and faces rising costs, labors and challenges. Therefore, computational drug design assists to defeat these difficulties and is promising to meet the need for anti-Ebola medicines [16, 17]. As reported in many recent studies, docking based approaches have been effectively employed in drug development, for prediction of the potential ability of a given molecule to bind the other targets [18] and to provide productive results for accelerating identification and optimization of drug formulation [4].

Over the past decade, the pharmaceutical industry has come to appreciate the task of therapeutic peptides that can play in the improvement of medical needs and how this type of compounds can be either complement or preferable alternative to small molecules and other biological therapeutics [19]. Due to the particular features of protein-peptide interfaces (PPIs) the application of small molecules could be limited for target PPIs. Contact surfaces involved in PPIs are large in size and this resulted in small molecules not to be outstanding for modeling of new therapeutic drugs [20]. Adversely, peptide molecules are much more efficient to be developed for interaction with large and flat protein surfaces and appear to be better adaptive. In this regard natural or synthetic peptides that are capable of interfering with PPIs, termed interfering peptides (IPs), possess increasing application [21, 22]. Peptides have an extended history of avail in therapy and are recognized as being safe and well tolerated. Novel improvements in peptide administration, bio-delivery, safety and stability are also remarkable in the preference of peptidic drug design and formulation. IPs have the potential to modify various cellular processes and may affirm the idea that they would have a significant potential to become promptly valuable therapeutic instruments [22].

Cell-penetrating peptides or CPPs (also known as protein transduction domains) are short-length peptides, generally made up of 5–30 amino acids, which are able to pass drugs or CPP/cargo complexes across plasma membrane into the cells [23]. CPPs have tremendous potential for mimicking PPI and can be great options to be used as drugs. Several studies on CPPs are presently undergoing pre-clinical and clinical trials that will offer new treatment options in the near future [24]. For further information, examples of which studies are available on references [25–27].

In this in silico study we identified 25 cell penetrating peptides (CPPs) that have antiviral potentials. Using them, we deployed series of peptide-docking screening against Ebola virus proteins as a drug discovery approach to develop a potential treatment for Ebola virus disease.

*Docking-Based Screening of Cell-Penetrating Peptides with Antiviral Features and Ebola Virus… DOI: http://dx.doi.org/10.5772/intechopen.97222*
