Celastrol for COVID-19

The COVID-19 pandemic has had a significant and lasting impact on the world. Four years on, despite the existence of effective vaccines, the continuous emergence of new SARS-CoV-2 variants remains a challenge for long-term immunity. Additionally, there remain few purpose-built antivirals to protect individuals at risk of severe disease in the event of future coronavirus outbreaks. A promising mechanism of action for novel coronavirus antivirals is the inhibition of viral entry. To facilitate entry, the coronavirus spike glycoprotein interacts with angiotensin converting enzyme 2 (ACE2) on respiratory epithelial cells. Blocking this interaction and consequently viral replication may be an effective strategy for treating infection, however further research is needed to better characterize candidate molecules with antiviral activity before progressing to animal studies and clinical trials. In general, antiviral drugs are developed from purely synthetic compounds or synthetic derivatives of natural products such as plant secondary metabolites. While the former is often favored due to the higher specificity afforded by rational drug design, natural products offer several unique advantages that make them worthy of further study including diverse bioactivity and the ability to work synergistically with other drugs. Accordingly, there has recently been a renewed interest in natural product-derived antivirals in the wake of the COVID-19 pandemic. This review provides a summary of recent research into coronavirus entry inhibitors, with a focus on natural compounds derived from plants, honey, and marine sponges.

COVID-19 patients can exhibit a wide range of clinical manifestations affecting various organs and systems. Neurological symptoms have been reported in COVID-19 patients, both during the acute phase of the illness and in cases of long-term COVID. Moderate symptoms include ageusia, anosmia, altered mental status, and cognitive impairment, and in more severe cases can manifest as ischemic cerebrovascular disease and encephalitis. In this narrative review, we delve into the reported neurological symptoms associated with COVID-19, as well as the underlying mechanisms contributing to them. These mechanisms include direct damage to neurons, inflammation, oxidative stress, and protein misfolding. We further investigate the potential of small molecules from natural products to offer neuroprotection in models of neurodegenerative diseases. Through our analysis, we discovered that flavonoids, alkaloids, terpenoids, and other natural compounds exhibit neuroprotective effects by modulating signaling pathways known to be impacted by COVID-19. Some of these compounds also directly target SARS-CoV-2 viral replication. Therefore, molecules of natural origin show promise as potential agents to prevent or mitigate nervous system damage in COVID-19 patients. Further research and the evaluation of different stages of the disease are warranted to explore their potential benefits.

Abstract: Acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the recent pandemic and worldwide outbreak of respiratory disease. Since there are no known specific drugs for fighting this virus and the process for new drug development is lengthy, scientists have been trying to develop drugs against this viral infection. The potent antiviral activity of natural products has been confirmed in several previous studies. Viral and host proteins contributing to COVID-19 infections can be targeted by natural compounds derived from plants, marine organisms, and microorganisms. The most important of these compounds are polyphenols (e.g., anthraquinone polyphenol, hinokinin, curcumin, and epigallocatechin gallate), alkaloids (e.g., isoquinoline, 10- hydroxyusambarensine, anisotine, and adhatodine), and terpenoids (salvinorin A, thymoquinone, bilobalide, ginkgolide A, and celastrol) from plants, sulphated polysaccharides (carrageenans, chondroitin sulfate C, and fucoidan) from marine organisms, and glycocin F and lactococcin G phycocyanin, and lipopeptide from microorganisms. This study reviews these compounds and their mechanism of action for treating COVID-19 infection and guides researchers in developing effective and safe therapeutic agents against this disease from naturally derived compounds.