Tyrocidine A 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.

The COVID-19 pandemic has underscored the need for effective and affordable antiviral drugs. Anthropogenic activities have increased interactions among humans, animals, and wildlife, contributing to the emergence of new and re-emerging viral diseases. RNA viruses pose significant challenges due to their rapid mutation rates, high transmissibility, and ability to adapt to host immune responses and antiviral treatments. The World Health Organization has identified several diseases (COVID-19, Ebola, Marburg, Zika, and others), all caused by RNA viruses, designated as being of priority concern as potential causes of future pandemics. Despite advances in antiviral treatments, many viruses lack specific therapeutic options, and more importantly, there is a paucity of broad-spectrum antiviral drugs. Additionally, the high costs of current treatments such as Remdesivir and Paxlovid highlight the need for more affordable antiviral drugs. Cyclic peptides from natural sources or designed through molecular modeling have shown promise as antiviral drugs with stability, low toxicity, high target specificity, and low antiviral resistance properties. This review emphasizes the urgent need to develop specific and broad-spectrum antiviral drugs and highlights cyclic peptides as a sustainable solution to combat future pandemics. Further research into these compounds could provide a new weapon to combat RNA viruses and address the gaps in current antiviral drug development.