Cyclosporine A for COVID-19

The severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has infected over 100 million people globally due to its high infectivity. After decades of efforts on the studies of nanomaterials, researchers have applied nanomaterials‐based strategies to combat the pandemic of the coronavirus disease 2019 (COVID‐19). First, nanomaterials facilitate the development of easy, fast, and low‐cost diagnostic assays to detect SARS‐CoV‐2 and related biomarkers. Second, nanomaterials enable the efficient delivery of viral antigens to antigen‐presenting cells or serve as adjuvants in the host, leading to vaccine development at an unprecedented pace. Lastly, nanomaterials‐based treatments may inhibit SARS‐CoV‐2 replication and reduce inflammation. Overall, nanomaterials have played important roles in controlling this COVID‐19 pandemic. Here, we provide a brief overview of the representative examples of nanomaterials‐based diagnostics, vaccines, and therapeutics in the fight against COVID‐19. The use and effectiveness of state responses is constantly evolving, particularly in relation to physical distancing policies during the COVID-19 pandemic. Testing is a measure of response performance and will be a central point during the infectious disease pandemic as all countries face similar situations. COVID-19 is a unique opportunity to assess and measure the success of a country, control its spread, and combat the social and economic impacts of interventions. By fighting the factors associated with testing and reporting, understanding the limits on COVID-19 case numbers will strengthen the country’s response to these and future pandemics, and improve the reliability of the knowledge gained by cross-country comparisons. With amazing and amazing COVID-19, a lack of testing may not trust the efforts of the entire community, rather than the entire population. The emergence of novel strains of SARS-CoV-2 highlights the pressing need to investigate various strategies for enhancing pandemic resilience. Even though tried-and-true methods like social separation, masks, and vaccinations have proven effective, issues with immunizations make finding a global answer more complex. This paper underscores the pivotal connection between immunological resilience and vitamins, shedding light on the compromised immune response resulting from undernourishment. Vitamins become essential for protecting the body from viral invasion, particularly from SARS-CoV-2. Crucial roles in cellular activities are played by vitamin A, which is necessary for vision, and the B-vitamin complex, which supports energy synthesis and nerve function. In the context of viral infections, the significance of vitamin D, crucial for both immune system function and bone health, along with vitamin C and its ability to combat free radicals, becomes paramount.This research aims to to elucidate the specific effects and mechanisms by which essential vitamins (A, B, C, D, and E) contribute to the mitigation of..

ABSTRACT SARS-CoV-2, the causative agent of COVID-19, has been intensely studied in search of effective antiviral treatments. The immunosuppressant cyclosporine A (CsA) has been suggested to be a pan-coronavirus inhibitor, yet its underlying mechanism remained largely unknown. Here, we found that non-structural protein 1 (Nsp1) of SARS-CoV-2 usurped CsA-suppressed nuclear factor of activated T cells (NFAT) signaling to drive the expression of cellular DEAD-box helicase 5 (DDX5), which facilitates viral replication. Nsp1 interacted with calcineurin A (CnA) to displace the regulatory protein regulator of calcineurin 3 (RCAN3) of CnA for NFAT activation. The influence of NFAT activation on SARS-CoV-2 replication was also validated by using the Nsp1-deficient mutant virus. Calcineurin inhibitors, such as CsA and VIVIT, inhibited SARS-CoV-2 replication and exhibited synergistic antiviral effects when used in combination with nirmatrelvir. Our study delineated the molecular mechanism of CsA-mediated inhibition of SARS-CoV-2 replication and the anti-SARS-CoV-2 action of calcineurin inhibitors. IMPORTANCE Cyclosporine A (CsA), commonly used to inhibit immune responses, is also known to have anti-SARS-CoV-2 activity, but its mode of action remains elusive. Here, we provide a model to explain how CsA antagonizes SARS-CoV-2 through three critical proteins: DDX5, NFAT1, and Nsp1. DDX5 is a cellular facilitator of SARS-CoV-2 replication, and NFAT1 controls the production of DDX5. Nsp1 is a viral protein absent from the mature viral particle and capable of activating the function of NFAT1 and DDX5. CsA and similar agents suppress Nsp1, NFAT1, and DDX5 to exert their anti-SARS-CoV-2 activity either alone or in combination with Paxlovid.

Abstract Background The active pursuit of network medicine for drug repurposing, particularly for combating Covid-19, has stimulated interest in the concept of structural controllability in cellular networks. We sought to extend this theory, focusing on the defense rather than control of the cell against viral infections. Accordingly, we extended structural controllability to total structural controllability and introduced the concept of control hubs. Perturbing any control hub may render the cell uncontrollable by exogenous stimuli like viral infections, so control hubs are ideal drug targets. Results We developed an efficient algorithm to identify all control hubs, applying it to a largest homogeneous network of human protein interactions, including interactions between human and SARS-CoV-2 proteins. Our method recognized 65 druggable control hubs with enriched antiviral functions. Utilizing these hubs, we categorized potential drugs into four groups: antiviral and anti-inflammatory agents, drugs acting on the central nervous system, dietary supplements, and compounds enhancing immunity. An exemplification of our approach’s effectiveness, Fostamatinib, a drug initially developed for chronic immune thrombocytopenia, is now in clinical trials for treating Covid-19. Preclinical trial data demonstrated that Fostamatinib could reduce mortality rates, ICU stay length, and disease severity in Covid-19 patients. Conclusions Our findings confirm the efficacy of our novel strategy that leverages control hubs as drug targets. This approach provides insights into the molecular mechanisms of potential therapeutics for Covid-19, making it a valuable tool for interpretable drug discovery. Our new approach is general and applicable to repurposing drugs for other diseases.