In the present work, the fruits of four Morus species, namely Morus alba (white mulberry), Morus nigra (black mulberry), Morus laevigata (large white fruit), and Morus laevigata (large black fruit), were analyzed for proximate composition, essential minerals, and antioxidant potentials. For this purpose, the ripe fruits were collected from the northern regions of Pakistan. The major nutritional components (moisture, ash, lipids, proteins, fibres, carbohydrates, and total sugar) were found to be in the suitable range along with good computed energy. Total dry weight, pH, and titratable acidity (percent citric acid) were (17.60±1.94)–(21.97±2.34) mg/100 g, (3.20±0.07)–(4.78±0.15), and (0.84±0.40)%–(2.00±0.08)%, respectively. Low riboflavin (vitamin B₂) and niacin (vitamin B₃) contents were recorded in all the fruits, while ascorbic acid (vitamin C) was in the range from (15.20±1.25) to (17.03±1.71) mg/100 g fresh weight (FW). The mulberry fruits were rich with regard to the total phenol and alkaloid contents, having values of (880±7.20)–(1650±12.25) mg/100 g FW and (390±3.22)–(660±5.25) mg/100 g FW, respectively. Sufficient quantities of essential macro-(K, Ca, Mg, and Na) and micro-(Fe, Zn, and Ni) elements were found in all the fruits. K was the predominant element with concentration ranging from (1270±9.36) to (1731±11.50) mg/100 g, while Ca, Na, and Mg contents were (440±3.21)–(576±7.37), (260±3.86)–(280±3.50), and (240±3.51)–(360±4.20) mg/100 g, respectivly. The decreasing order of micro-minerals was Fe>Zn>Ni. The radical scavenging activity of methanolic extract of fruits was concentration-dependent and showed a correlation with total phenolic constituents of the respective fruits. Based on the results obtained, mulberry fruits were found to serve as a potential source of food diet and natural antioxidants.

Phosphodiesterases (PDEs) are vital in signal transduction, specifically by hydrolyzing cAMP and cGMP. Within the PDE family, PDE10A is notable for its prominence in the striatum and its regulatory function over neurotransmitters in medium-spiny neurons. Given the dopamine deficiency in Parkinson's disease (PD) that affects striatal pathways, PDE10A inhibitors could offer therapeutic benefits by modulating D1 and D2 receptor signaling. This study was motivated by the successful history of quinazoline/quinazoline scaffolds in the inhibition of PDE10A. This study involved detailed in silico evaluations through docking followed by pharmacological, pharmacophoric, and pharmacokinetic analyses, prioritizing central nervous system (CNS)-active drug criteria. Seven cyclic peptides, those featuring the quinazoline/quinazoline moiety at both termini, exhibited notably enhanced docking scores compared to those of the remaining alkaloids within the screened library. We identified 7 quinolines and 1 quinazoline including Lepadin G, Aspernigerin, CJ-13536, Aurachin A, 2-Undecyl-4(1H)-quinolone, Huajiaosimuline 3-Prenyl-4-prenyloxyquinolin-2-one, and Isaindigotone that followed the standard CNS active drug criteria. The dominant quinoline ring in our study and its related quinazoline were central to our evaluations; therefore, the pharmacophoric features of these scaffolds were highlighted. The top alkaloids met all CNS-active drug properties; while nonmutagenic and without PAINS alerts, many indicated potential hepatotoxicity. Among the compounds, Huajiaosimuline was particularly significant due to its alignment with lead-likeness and CNS-active criteria. Aspernigerin demonstrated its affinity for numerous dopamine receptors, which signifies its potential to alter dopaminergic neurotransmission that is directly related to PD. Interestingly, the majority of these alkaloids had biological targets primarily associated with G protein-coupled receptors, critical in PD pathophysiology. They exhibit superior excretion parameters and toxicity end-points compared to the standard. Notably, selected alkaloids demonstrated stability in the binding pocket of PDE10A according to the molecular dynamic simulation results. Our findings emphasize the potential of these alkaloids as PDE10A inhibitors. Further experimental studies may be necessary to confirm their actual potency in inhibiting PDE10A before exploring their therapeutic potential in PD.

Severe Acute Respiratory Syndrome Corona Virus (SARS-CoV-2) is the causative agent of COVID-19 pandemic, which has resulted in global fatalities since late December 2019. Alkaloids play a significant role in drug design for various antiviral diseases, which makes them viable candidates for treating COVID-19. To identify potential antiviral agents, 102 known alkaloids were subjected to docking studies against the two key targets of SARS-CoV-2, namely the spike glycoprotein and main protease. The spike glycoprotein is vital for mediating viral entry into host cells, and main protease plays a crucial role in viral replication; therefore, they serve as compelling targets for therapeutic intervention in combating the disease. From the selection of alkaloids, the top 6 dual inhibitory compounds, namely liensinine, neferine, isoliensinine, fangchinoline, emetine, and acrimarine F, emerged as lead compounds with favorable docked scores. Interestingly, most of them shared the bisbenzylisoquinoline alkaloid framework and belong to Nelumbo nucifera, commonly known as the lotus plant. Docking analysis was conducted by considering the key active site residues of the selected proteins. The stability of the top three ligands with the receptor proteins was further validated through dynamic simulation analysis. The leads underwent ADMET profiling, bioactivity score analysis, and evaluation of drug-likeness and physicochemical properties. Neferine demonstrated a particularly strong affinity for binding, with a docking score of -7.5025 kcal/mol for main protease and -10.0245 kcal/mol for spike glycoprotein, and therefore a strong interaction with both target proteins. Of the lead alkaloids, emetine and fangchinoline demonstrated the lowest toxicity and high LD50 values. These top alkaloids, may support the body’s defense and reduce the symptoms by their numerous biological potentials, even though some properties naturally point to their direct antiviral nature. These findings demonstrate the promising anti-COVID-19 properties of the six selected alkaloids, making them potential candidates for drug design. This study will be beneficial in effective drug discovery and design against COVID-19 with negligible side effects.