Transmembrane serine protease 2 (TMPRSS2) has been established as one of the host proteins that facilitate entry of coronaviruses into host cells. One of the approaches often employed towards preventing the entry and proliferation of viruses is computer-aided inhibition studies to identify potent compounds that can inhibit activity of viral targets in the host through binding at the active site. In this study, we developed a pharmacophore model of reportedly potent drugs against severe acute respiratory syndrome coronaviruses 1 and 2 (SARS-CoV-1 and-2). The model was used to screen the ZINC database for commercially available compounds having similar features with the experimentally tested drugs. The top 3000 compounds retrieved were docked into the active sites of a homologymodelled TMPRSS2. Docking scores of the top binders were validated and the top-ranked compounds were subjected to ADME, Lipinski's and medicinal Chemistry property predictions for druglikeness analyses. Two lead compounds, ZINC64606047 and ZINC05296775, were identified having binding affinities higher than those of the reference inhibitors, favorable interactions with TMPRSS2 active site residues and good ADME and medicinal chemistry properties. Molecular dynamics simulation was used to assess the stability and dynamics of the interactions of these compounds with TMPRSS2. Binding free energy and contribution energy evaluations were determined using MMPBSA method. Analyses of the trajectory dynamics collectively established further that the lead compounds bound and interacted stably with active site residues of TMPRSS2. Nonetheless, experimental studies are needed to further assess the potentials of these compounds as possible therapeutics against coronaviruses.

This study investigated the in vitro antihypertensive, antiradical and hydrogen peroxidescavenging properties of protein hydrolysates from Citrullus lanatus (watermelon) seed (CSPHs) obtained through enzymatic digestion. Proteins from watermelon seeds were isolated and enzymatically hydrolyzed with non-specific (alcalase), moderately specific (pepsin) and highly specific (trypsin) proteases, mimicking human gastrointestinal digestion. The hydrolysates were investigated for inhibitory property against angiotensin-I-converting enzyme (ACE) activity. Using N-[3-(2furyl)acryloyl]-L-phenylalanyl-glycyl-glycine as the substrate, CSPHs showed concentration-dependent ACE inhibition (IC 50 1.377-1.757 mg/mL) with peptic CSPH having the strongest ACE-inhibition followed by tryptic CSPH. Kinetic analysis revealed that peptic CSPH inhibited ACE activity in a mixedtype inhibition pattern while alcalase and tryptic CSPHs exhibited non-competitive inhibition mode. Peptic CSPH demonstrated the strongest DPPH radical-scavenging activity while tryptic CSPH showed the highest H 2 O 2-scavenging property. These results show that protein hydrolysates from watermelon seed possess bioactivities that could be exploited in the management of hypertension.

Neem ( Azadirachta indica ) seed protein hydrolysates were investigated for in vitro antioxidant and angiotensin 1-converting enzyme (ACE)-inhibitory activities. Neem seed proteins were hydrolysed using pepsin, trypsin and Alcalase. The degree of pepsin hydrolysis of neem seed protein was significantly higher (p < 0.05) than those of trypsin and Alcalase hydrolysis. Proteolytic hydrolysis of the isolate resulted in hydrolysates with improved Arg/Lys ratio, with pepsin hydrolysates still being able to maintain an acceptable level of essential amino acids comparable to that of the isolate. At 2.5 mg/mL, pepsin neem seed protein hydrolysate (NSPH) demonstrated the strongest antioxidant activity with 67.15 % and 50.07 % DPPH- and superoxide anion radical-scavenging activities, respectively, while trypsin NSPH had the highest ferric-reducing power. Using N-[3-(2-furyl)acryloyl]-L-phenylalanyl-glycyl-glycine (FAPGG) as substrate, NSPHs strongly inhibited ACE (69.20–80.39 %) in a concentration-dependent manner. Pepsin NSPH had higher ACE-inhibitory activity than trypsin and Alcalase NSPHs. Kinetic studies showed the mechanism of ACE inhibition to be mixed-type with Ki values of 0.62, 0.84, 1.5 for pepsin, trypsin and alcalase NSPH, respectively. These results suggest that NSPH can be used as a potential nutraceutical with antioxidant capacity and inhibitory activity against ACE.

The antidiabetic, normolipidaemic, antioxidant and safety evaluations of ethanolic extract of Acacia ataxacantha roots (EEAAR) were investigated in streptozotocin -induced diabetic rats, to verify its use in traditional African medicine and as alternative to synthetic normoglycaemic agents in diabetic treatments. Thirty albino rats (Rattus novergicus) were randomized into six groups -control, diabetic control, EEAAR-treated at 125 mg/kg, 250 mg/kg, 500 mg/kg body weights (b.wts.) and metformin groups, respectively. Phytochemical screening showed the presence of alkaloids, polyphenols, flavonoid, saponins, tannins and terpenoid. Blood glucose was significantly reduced (p < 0.05) especially after 7 days of oral administration of EEAAR at 125 mg/kg b.wt with values (110.01 ± 9.64 mg/dl) similar to that of the control (106.33 ± 4.13 mg/dl). There was an increase (p < 0.05) in the ALT and AST activities of the liver and serum of rats in all the groups except in those that received 125 mg/kg b.wt. Serum total cholesterol, low density lipoprotein cholesterol and triglyceride were decreased (p < 0.05) upon administration of the extract and metformin. There was no difference (p > 0.05) in malondialdehyde concentration of rats administered with 125 mg/kg b.wt. of extract and metformin. Superoxide dismutase activity was elevated (p < 0.05) in all groups and compared favourably with the control in each of the tissues. This study revealed the antidiabetic and hypolipidaemic effects of EEAAR, which may be due to the antioxidant properties of some of the phytochemical constituents. However, the extract may not be safe at large and repeated doses.