Mucuna pruriens seeds have been widely used against snakebite in traditional medicine. The antivenin property of a water extract of seeds was assessed in vivo in mice. The serum of mice treated with extract was tested for its immunological properties. Two proteins of Echis carinatus venom with apparent molecular masses of 25 and 16 kDa were detected by Western blot analysis carried out using IgG of mice immunized with extract or its partially purified protein fractions. By enzymatic in-gel digestion and electrospray ionization-mass spectrometry/mass spectrometry analysis of immunoreactive venom proteins, phospholipase A 2, the most toxic enzyme of snake venom, was identified. These results demonstrate that the observed antivenin activity has an immune mechanism. Antibodies of mice treated with non-lethal doses of venom reacted against some proteins of M. pruriens extract. Proteins of E. carinatus venom and M. pruriens extract have at least one epitope in common as confirmed by immunodiffusion assay.Snakebite is a considerable problem in certain tropical and subtropical countries. According to World Health Organization estimates, 40,000 of 5 million cases of snakebite are fatal. Antivenins obtained from horses treated with snake venom are one of the principal remedies against snakebite. This therapy has the disadvantage that antivenins must be given immediately, and snakebite victims may develop an adverse reaction including anaphylactic shock (1). The use of endogenous plants with a reputation against snakebite is therefore worth considering (2).In preliminary experiments (3, 4) we demonstrated that extract of M. pruriens (MPE), 1 a medicinal plant widely used in Nigeria for its chemical and pharmacological properties, protects mice against the lethal effect of Echis carinatus venom (EV). Both MPE and EV are heterogeneous mixtures, their interaction represents a complex phenomenon, and there is no information about its biochemical mechanism. EV contains proteins with different toxic properties including opposite effects on blood clotting. Well known proteins are: disintegrins EC3 (5), EC6 (6), and echistatin (7), which inhibit the interaction of fibrinogen with the glycoprotein IIb-IIIa receptor on the platelet surface; echicetin (8) and ECLVIX/Xbp (9) with an opposite effect on platelet aggregation; two metalloproteases, ecarin (10, 11) and carinactivase (12), which are prothrombin activators and act as procoagulant enzymes; and phospholipase A 2 (PLA 2 ) (13-15), the most abundant enzyme, which has many effects including inhibition of prothrombin activation by ecarin and carinactivase (16). When injected into mice, this complex mixture of proteins induces disseminated intravascular coagulation leading to death in less than a day. The composition of the M. pruriens seed is also complex and variable, with 20 -30% protein (lectins, globulins, protease inhibitors), 1-10% fat, 4 -5% ash, 4 -9% water, 4 -7% fiber (17-20), and L-DOPA (21), an interesting non-protein component. The aim of the present study was to stud...
Background: The coronavirus spike (S) glycoprotein and M protease are two key targets that have been identified for vaccines and drug development against COVID-19. Methods: Virtual screening of some compounds of plant origin that have shown antiviral activities were carried out on the two targets, the M protease (PDB ID 6LU7) and S glycoprotein (PDB ID 6VSB), by docking with PyRx software. The binding affinities were compared with other compounds and drugs already identified as potential ligands for the M protease and S glycoprotein, as well as chloroquine and hydroxychloroquine. The docked compounds with best binding affinities were also filtered for drug likeness using the SwissADME and PROTOX platforms on the basis of physicochemical properties and toxicity, respectively. Results: The docking results revealed that scopadulcic acid and dammarenolic acid had the best binding affinity for the S glycoprotein and Mpro protein targets, respectively. Silybinin, through molecular docking, also demonstrated good binding affinity for both protein targets making it a potential candidate for further evaluation as repurposed candidate for SARS-CoV-2, with likelihood of having multitarget activity as it showed activities for both targets. Conclusions: The study proposes that scopadulcic acid and dammarenolic acid be further evaluated in vivo for drug formulation against SARS-COV-2 and possible repurposing of Silybinin for the management of COVIV-19.
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