Leronlimab, PA14, PRO-140, Vyrologix for COVID-19

ABSTRACT Background and Aim Post‐acute sequelae of SARS‐CoV‐2 infection (PASC), commonly referred to as long COVID, has emerged as a significant global health concern, marked by persistent symptoms and chronic inflammation following recovery from acute COVID‐19. A central driver of PASC pathogenesis is the sustained cytokine storm—an exaggerated and prolonged pro‐inflammatory response that leads to ongoing tissue injury and multisystem dysfunction. This review aims to synthesize current knowledge on cytokine dysregulation in PASC and evaluate emerging therapeutic strategies targeting these immunopathological mechanisms. Methods A narrative review methodology was employed, drawing from recent peer‐reviewed publications, clinical trial databases, and immunological studies published between 2020 and 2025. Articles focusing on cytokine profiles in PASC, immune reprogramming, and immunomodulatory therapies were included. Mechanistic studies, biomarker research, and translational trials involving corticosteroids, cytokine inhibitors, Janus kinase (JAK) inhibitors, and novel biologics were critically analyzed. Results The literature reveals that elevated levels of IL‐6, IL‐1β, TNF‐α, and IFN‐γ persist in a subset of PASC patients, contributing to chronic systemic and organ‐specific inflammation. Emerging therapies—including IL‐6 and IL‐1 receptor antagonists, JAK inhibitors, and CNS‐penetrant anti‐inflammatory agents—demonstrate promise in modulating cytokine storms and improving clinical outcomes. Recent insights into cytokine profiling, trained immunity, and neuroimmune crosstalk suggest potential for precision‐based interventions tailored to distinct inflammatory phenotypes in PASC. Conclusion Persistent cytokine dysregulation underlies the pathophysiology of PASC and offers actionable targets for therapeutic intervention. Immunomodulatory strategies, when guided by biomarker profiling and systems biology approaches, hold promise for mitigating long‐term complications of COVID‐19. Future research should prioritize personalized treatment algorithms to address the heterogeneity of PASC and enhance patient recovery.

According to the World Health Organization (WHO), in the second half of 2022, there are about 606 million confirmed cases of COVID-19 and almost 6,500,000 deaths around the world. A pandemic was declared by the WHO in March 2020 when the new coronavirus spread around the world. The short time between the first cases in Wuhan and the declaration of a pandemic initiated the search for ways to stop the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or to attempt to cure the disease COVID-19. More than ever, research groups are developing vaccines, drugs, and immunobiological compounds, and they are even trying to repurpose drugs in an increasing number of clinical trials. There are great expectations regarding the vaccine’s effectiveness for the prevention of COVID-19. However, producing sufficient doses of vaccines for the entire population and SARS-CoV-2 variants are challenges for pharmaceutical industries. On the contrary, efforts have been made to create different vaccines with different approaches so that they can be used by the entire population. Here, we summarize about 8162 clinical trials, showing a greater number of drug clinical trials in Europe and the United States and less clinical trials in low-income countries. Promising results about the use of new drugs and drug repositioning, monoclonal antibodies, convalescent plasma, and mesenchymal stem cells to control viral infection/replication or the hyper-inflammatory response to the new coronavirus bring hope to treat the disease.

Viruses with rapid replication and easy mutation can become resistant to antiviral drug treatment. With novel viral infections emerging, such as the recent COVID-19 pandemic, novel antiviral therapies are urgently needed. Antiviral proteins, such as interferon, have been used for treating chronic hepatitis C infections for decades. Natural-origin antimicrobial peptides, such as defensins, have also been identified as possessing antiviral activities, including direct antiviral effects and the ability to induce indirect immune responses to viruses. To promote the development of antiviral drugs, we constructed a data repository of antiviral peptides and proteins (DRAVP). The database provides general information, antiviral activity, structure information, physicochemical information, and literature information for peptides and proteins. Because most of the proteins and peptides lack experimentally determined structures, AlphaFold was used to predict each antiviral peptide’s structure. A free website for users (http://dravp.cpu-bioinfor.org/, accessed on 30 August 2022) was constructed to facilitate data retrieval and sequence analysis. Additionally, all the data can be accessed from the web interface. The DRAVP database aims to be a useful resource for developing antiviral drugs.