Exploring the Impact of Fucoidan on COVID-19: A Detailed Analysis of Its Role in SARS-CoV-2 Infection and Immune Response


The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, first emerged in Wuhan, Hubei Province, China in December 2019, marking the beginning of a global health crisis (Zhou et al., 2020). As of August 2023, the pandemic has resulted in over 693 million confirmed cases and at least 6.9 million deaths, significantly impacting the global economy. Characterized by symptoms such as dry cough, dyspnea, fever, and bilateral lung infiltration, COVID-19 shares similarities with the earlier SARS-CoV (Lu et al., 2020).

The evolution of the virus saw the emergence of various variants of concern (VOCs), such as Alpha, Beta, Gamma, Delta, and Omicron, each with unique transmissibility and virulence profiles (Richardson et al., 2022). The Omicron variant, notable for its extensive mutations, became predominant globally, exhibiting higher infectivity but lower virulence and mortality rates than its predecessors (Scovino et al., 2022).

SARS-CoV-2 comprises structural proteins crucial for its entry and assembly, including the spike (S), envelope (E), membrane (M), and nucleocapsid (N) proteins (Lu et al., 2020; Shi et al., 2022; Zhou et al., 2020). The S protein, in particular, is a primary target for therapeutic interventions and vaccine development (Jackson, Farzan, Chen, & Choe, 2022). The virus utilizes the angiotensin-converting enzyme 2 (ACE2) as its entry receptor, with the endogenous transmembrane protease serine 2 facilitating the fusion of viral and cellular membranes (Shang et al., 2020).

ACE2 is present in various human tissues, including the lungs, heart, brain, liver, kidneys, intestines, and testes (Gheblawi et al., 2020). Interestingly, SARS-CoV-2 not only triggers inflammation but also alters gut microbiota, with studies indicating the role of ACE2 in intestinal inflammation and microbiota ecology (Zhang et al., 2023; Amirian, 2020; Hashimoto et al., 2012; Viana, Nunes, & Reis, 2020).

Fucoidan, a sulfated polysaccharide predominantly composed of fucose, has garnered attention due to its diverse biological activities, including anti-inflammatory, antiviral, antioxidant, hypolipidemic, immunomodulatory, and anticancer effects (Li et al., 2008a; Jayawardena et al., 2019; Oliyaei, Moosavi-Nasab, & Mazloomi, 2022; Lean et al., 2015; Diaz-Resendiz et al., 2022; Koike et al., 2021; Marudhupandi et al., 2014; Wei et al., 2019; Zhang, Oda, Yu, & Jin, 2015; Anastyuk et al., 2017).

Its potential in directly inhibiting viral replication and stimulating immune responses has been noted in recent research (Richards et al., 2020). Various studies have explored the antiviral properties of fucoidan and its derivatives, demonstrating their efficacy in preventing viral infection by hindering viral adsorption and entry into host cells (Koike et al., 2021; Tandon et al., 2021; You et al., 2022; Song et al., 2018; Kwon et al., 2020).

Our current study delves into the chemical structures of fucoidan from Ascophyllum nodosum (FUCA) and Undaria pinnatifida (FUCU), examining their influence on ACE2 mRNA and protein expression in vivo and in vitro. Utilizing a Syrian hamster model of SARS-CoV-2 infection, we assessed the antiviral efficacy of FUCA and FUCU based on cytokine expression changes. Additionally, we employed 16S rRNA high-throughput sequencing to evaluate the effects of these compounds on human and hamster gut microbiota. Our findings suggest that fucoidan could be a promising dietary supplement for its potential anti-SARS-CoV-2 activity, warranting further in-depth research.

In conclusion, the COVID-19 pandemic, with its evolving variants and global impact, continues to challenge the scientific community. This study contributes to the ongoing efforts to understand and mitigate the effects of SARS-CoV-2, highlighting the potential of natural compounds like fucoidan in managing the pandemic. As the world continues to adapt and respond to this health crisis, studies such as ours provide valuable insights into novel therapeutic strategies against COVID-19.



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