A global health concern has emerged as a response to the recent SARS-CoV-2 pandemic. The identification and inhibition of drug targets of SARS-CoV-2 is a decisive obligation of scientists. In addition to the cell entry mechanism, SARS-CoV-2 expresses a complicated replication mechanism that provides excellent drug targets. Papain-like protease (PL^pro) and 3-chymotrypsin-like protease (3CL^pro) play a vital role in polyprotein processing, producing functional non-structural proteins essential for viral replication and survival in the host cell. Moreover, PL^pro is employed by SARS-CoV-2 for reversing host immune responses. Therefore, if some particular compound has the potential to interfere with the proteolytic activities of 3CL^pro and PL^pro of SARS-CoV-2, it may be effective as a treatment or prophylaxis for COVID-19, reducing viral load, and reinstating innate immune responses. Thus, the present study aims to inhibit SARS-CoV-2 through 3CL^pro and PL^pro using marine natural products isolated from marine algae that contain numerous beneficial biological activities. Molecular docking analysis was utilized in the present study for the initial screening of selected natural products depending on their 3CL^pro and PL^pro structures. Based on this approach, Ishophloroglucin A (IPA), Dieckol, Eckmaxol, and Diphlorethohydroxycarmalol (DPHC) were isolated and used to perform in vitro evaluations. IPA presented remarkable inhibitory activity against interesting drug targets. Moreover, Dieckol, Eckmaxol, and DPHC also expressed significant potential as inhibitors. Finally, the results of the present study confirm the potential of IPA, Dieckol, Eckmaxol, and DPHC as inhibitors of SARS-CoV-2. To the best of our knowledge, this is the first study that assesses the use of marine natural products as a multifactorial approach against 3CL^pro and PL^pro of SARS-CoV-2.

Sargassum horneri (SH), a marine brown alga, is known to contain a variety of bioactive ingredients and previous studies reported sulfated polysaccharides in SH as a potential candidate for a functional ingredient.

The aim of this study was to assess the potential hypertensive effects of the IGTGIPGIW peptide purified from Hippocampus abdominalis alcalase hydrolysate (HA) for application in the functional food industry. We investigated the antihypertensive effects of IGTGIPGIW in vitro by assessing nitric oxide production in EA.hy926 endothelial cells, which is a major factor affecting vasorelaxation. The potential vasorelaxation effect was evaluated using 4-amino-5-methylamino-2′,7′-difluorofluorescein diacetate, a fluorescent stain. IGTGIPGIW significantly increased the expression of endothelial-derived relaxing factors, including endothelial nitric oxide synthase and protein kinase B, in EA.hy926 cells. Furthermore, oral administration of IGTGIPGIW significantly lowered the systolic blood pressure (183.60 ± 1.34 mmHg) and rapidly recovered the diastolic blood pressure (143.50 ± 5.55 mmHg) in the spontaneously hypertensive rat model in vivo. Our results demonstrate the antihypertensive activity of the IGTGIPGIW peptide purified from H. abdominalis and indicate its suitability for application in the functional food industry.

Microgravity stimulation is associated with retinal pigment epithelial (RPE) cells that transition to mesenchymal cells (EMT), and these pathological changes cause visual impairment. Vascular endothelial growth factor (VEGF) is produced from the RPE and contributes to photoreceptor survival. However, changes in VEGF production and function under microgravity stimulation are unknown. In this study, we verified that microgravity stimulation changed the morphological characteristics of human RPE cells (ARPE19 cells) and the expression of actin cytoskeleton regulators, which are related to excessive VEGF expression. Interestingly, microgravity stimulation increased not only the production of VEGF but also the expression of EMT markers. Previously, we studied the potential of ishophloroglucin A (IPA), a phlorotannin, as an antioxidant. In silico results confirmed that IPA could structurally bind to VEGF receptor 2 (VEGFR2) among VEGFRs and inhibit the VEGF pathway. IPA significantly decreased VEGF production and EMT marker expression in microgravity-stimulated cells. It also significantly reduced excessive cell migration in VEGF-induced EMT. Overall, our findings suggested that IPA treatment decreased VEGF production and EMT marker expression in microgravity-stimulated or VEGF-treated ARPE19 cells, and this decrease in EMT could restore excessive cell migration by inhibiting the VEGF/VEGFR2 pathway. Therefore, it is a potential therapeutic candidate for angiogenesis-related eye diseases.

Fisheries and Aquatic Sciences