Cyanovirin-N for COVID-19

Abstract Marine ecosystems are a vast, underexplored reservoir of bioactive compounds with unique structural diversity and potent biological activities. Enveloped viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, continue to pose significant global health threats, exacerbated by emerging variants, limited therapeutic options beyond vaccines, and challenges such as drug resistance and immune dysregulation. Compounds derived from marine organisms, including lectins (e.g., griffithsin from red algae Griffithsia sp .), sulfated polysaccharides (e.g., iota-carrageenan from red algae Chondrus crispus ), polyphenols (e.g., dieckol from brown algae Ecklonia cava ), and depsipeptides (e.g., plitidepsin from tunicates), have shown promising antiviral effects in preclinical studies. These molecules primarily act by inhibiting viral entry (via the spike glycoprotein or glycan binding), replication (targeting proteases such as the main protease [Mpro] and the RNA-dependent RNA polymerase [RdRp]), or by modulating host immune responses (e.g., reducing cytokine storms or oxidative stress). In vitro, in vivo, and in silico evidence highlights their potential against SARS-CoV-2 and related enveloped viruses (e.g., HIV, HSV, influenza, HCMV), which share mechanistic similarities, including envelope-mediated fusion and RNA-based replication. This narrative review provides a cohesive overview of selected marine-derived bioactive compounds with reported activity against SARS-CoV-2 and other enveloped viruses. It examines their sources, structural features, mechanisms of action, key activity metrics (e.g., IC₅₀/EC₅₀ values), and translational prospects, and addresses challenges such as scalability, preclinical-to-clinical gaps, and sustainability aligned with the European Blue Economy. By integrating recent findings, this review aims to highlight promising leads and guide future research toward innovative, broad-spectrum antiviral therapies.

Since the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its resultant pneumonia in December 2019, the cumulative number of infected people worldwide has exceeded 670 million, with over 6.8 million deaths. Despite the marketing of multiple series of vaccines and the implementation of strict prevention and control measures in many countries, the spread and prevalence of SARS-CoV-2 have not been completely and effectively controlled. The latest research shows that in addition to angiotensin converting enzyme II (ACE2), dozens of protein molecules, including AXL, can act as host receptors for SARS-CoV-2 infecting human cells, and virus mutation and immune evasion never seem to stop. To sum up, this review summarizes and organizes the latest relevant literature, comprehensively reviews the genome characteristics of SARS-CoV-2 as well as receptor-based pathogenesis (including ACE2 and other new receptors), mutation and immune evasion, vaccine development and other aspects, and proposes a series of prevention and treatment opinions. It is expected to provide a theoretical basis for an in-depth understanding of the pathogenic mechanism of SARS-CoV-2 along with a research basis and new ideas for the diagnosis and classification, of COVID-19-related disease and for drug and vaccine research and development.