INTRODUCTION
Marburg virus (MARV) belongs to the family Filoviridae. MARV is pathogenic in humans, virulent, enveloped, and linear non-segmented RNA (Cross et al., 2021, Bozhanova et al., 2020, Kuhn et al., 2019, Li et al., 2019, Asad et al., 2020). Marburg virus was reported for the first time in Germany and later in the Democratic Republic of Congo (DRC). Its origin was a bat commonly found in Egypt called Rousettus aegyptiacus(Organization, 1978, Pigott et al., 2015, Koch et al., 2020, Schwartz, 2019). The recently reported outbreaks of MARV in DRC resulted in an approximately 81% mortality rate in about 26 months (August 2018 and May 2020) (Batra et al., 2020, Porter et al., 2020, Organization, 2019) (Asad et al., 2020, Kuhn et al., 2019, Nyakarahuka et al., 2019, Batra et al., 2020, Porter et al., 2020, Organization, 2019). The mode of infection of MARV is by direct contact with human blood and body fluids of an infected patient, contaminated objects, uncooked (Moreau et al., 2015), or partially cooked wildlife meat (Batra et al., 2020, Kuhn et al., 2019, Roels et al., 1999, Gałaś, 2014). After infection of MARV in patients, reported symptoms such as fever, sore throat, muscle pain, fatigue, headache and weakness with nausea, diarrhea, stomach pain and haematological irregularities have been observed (Pigott et al., 2015, Nyakarahuka et al., 2019, Uyeki et al., 2016, Kortepeter et al., 2011, Kortepeter et al., 2020, Chertow et al., 2014). The high mortality rate of the Marburg Virus Disease (MVD) has generated research interest to find a possible treatment. Currently, there are no approved FDA drugs for MVD. However, there are few anti-viral drugs such as FGI-103 (Warren et al., 2010), Favipiravir (T-705)(Zhu et al., 2018) and Remdesivir (GS‐5734) (Porter et al., 2020) that are being investigated as repurposed drugs (Pruijssers et al., 2020, Choy et al., 2020, Savarino et al., 2003, Dan et al., 2020, Colson et al., 2020, Barlow et al., 2020, Dong et al., 2020, Wang et al., 2020, Awadasseid et al., 2021, Goldman et al., 2021, Beigel et al., 2020, Brauburger et al., 2012).
Some medicinal plants, such as Spondias mombin Linn(S. mombin ), have been reported to have a wide range of anti-viral activity (Mukhtar et al., 2008). In our previous in silico study, Geraniin, a compound obtained from S. mombin leaf extracts, was reported to be a potential inhibitor candidate of EBOV secreted Glycoprotein (sGP) (Boadu et al., 2021). Geraniin was noted to possess anti-viral properties against Dengue type-2 (DENV-2), Zika (ZIKV), hepatitis B, herpes simplex type 1, and Coxsackie B viruses (Choi et al., 2019, Liu et al., 2016, Yang et al., 2007, Yang et al., 2012, Li et al., 2008, Siqueira et al., 2020, Ahmad et al., 2019, Haddad et al., 2020, Ahmad et al., 2017). Belonging to the family Anacardiaceae (Ayoka et al., 2006), S. mombin (SM) has been used in ethnomedicines in the treatment of viral ailments (Agra et al., 2007, Ademola et al., 2005, Amadi et al., 2007, Osuntokun et al., 2018, Shosan et al., 2014). Pharmacologically, leaf extracts of S. mombin indicate anti-viral, anti-oxidant, antimicrobial (Ajao et al., 1985), and anti-inflammatory properties (Sabiu et al., 2015, Ishola et al., 2018, Akinmoladun et al., 2015, Corthout et al., 1992, dos Santos Sampaio et al., 2018, Mahmood et al., 1997, Siqueira et al., 2020).
Ethnomedicinally, medicinal plants for decades have been used to manage diseases. However, the lack of proper documentation, standardization, and biosafety poses a significant challenge due to unknown or delayed side effects on patients (Birdi et al., 2006).
Bioactive phytochemical compounds from plants used ethnomedicinally, mostly prepared as crude extracts, have shown various pharmacological properties(Yuan et al., 2016, Anand et al., 2019, Pandey et al., 2008). Hence, to find the rationale for their pharmacological action, several analyses such as Gas- Chromatography-Mass Spectrometry (GC-MS) and computer-aided drug design technology, to mention a few are commonly used to identify possible bioactive drug candidates found in crude extracts of medicinal plants. GC-MS analysis is one of the fastest and accurate techniques and normally requires a small quantity of extract. Identification using GC-MS normally detects terpenes, alcohols and other smaller fragments(Razack et al., 2015, Keskes et al., 2017, Fan et al., 2018, Juszczak et al., 2019). Therefore, in the current study, GC–MS analysis was used to detect and identify antiviral phytochemical compounds obtained from leaf extracts of S. mombinand Geraniin; a tannin reported in the literature and our previous research to possess antiviral properties.
Currently, computer-aided techniques are being used in the prediction of drug candidates, from medicinal plant extracts by many pharmaceutical companies to reduce drug failures in the market and the cost of research due to poor pharmacokinetic properties(Fang et al., 2018). Therefore,in silico molecular docking, molecular simulation and pharmacokinetic analysis are used to obtain vital information, on predicting the therapeutic-target protein interactions(Bharathi et al., 2014, Lee and Kim, 2019, Sliwoski et al., 2014).
Considering the reported diverse pharmacological properties and broad-spectrum antiviral properties of S. mombin and compound it isolate such as Geraniin as well as our previous in silico study which identified Geraniin as a potential inhibitor candidate of EBOV secreted Glycoprotein (sGP) (Boadu et al., 2021),S mombin phytochemical compounds may be promising targets worth investigating further against other viruses. Hence the present study focused on the detection, identification of antiviral phytochemical compounds from alcoholic leaf extracts of S mombin and 1,2-Benzenedicarboxylic acid, butyl 2-methylpropyl ester, a fragment of Geraniin. Subsequently, all antiviral phytochemical compounds identified were subjected to, pharmacokinetics, molecular docking and molecular simulation using in silico techniques to investigate a possible anti-Filoviral therapeutic candidate against the Marburg virus (MARV VP35).