Capsaicin for COVID-19

The onset of the global pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in Wuhan in December 2019 has led to an urgent need for effective preventive and therapeutic solutions. Among the various approaches explored, natural products have shown potential in the fight against COVID-19. This study employed computational techniques to screen and evaluate six natural antiviral compounds for their effectiveness against the SARS-CoV-2 Main Protease (Mpro). By using molecular docking simulations, the interactions between these natural compounds and the target proteins were predicted and analyzed, focusing on factors such as binding affinity, interaction patterns, and structural compatibility within the active sites. The analysis indicated that Cladosin C and Rhodatin formed the most stable interactions with Mpro, engaging with several critical residues. Cannabidiol, Capsaicin, and Kappa-Carrageenan also demonstrated promising interactions, though with some variability. On the other hand, Astaxanthin exhibited the least stable binding, suggesting limited antiviral potential. This research provides insights into the possible roles of these natural compounds as antagonists of the SARS-CoV-2 Mpro enzyme. Further in vitro and in vivo studies are necessary to confirm the antiviral properties of these compounds, and future research should investigate their broader antiviral applications.

Natural products and plant extracts exhibit many biological activities, including that related to the defense mechanisms against parasites. Many studies have investigated the biological functions of secondary metabolites and reported evidence of antiviral activities. The pandemic emergencies have further increased the interest in finding antiviral agents, and efforts are oriented to investigate possible activities of secondary plant metabolites against human viruses and their potential application in treating or preventing SARS-CoV-2 infection. In this review, we performed a comprehensive analysis of studies through in silico and in vitro investigations, also including in vivo applications and clinical trials, to evaluate the state of knowledge on the antiviral activities of secondary metabolites against human viruses and their potential application in treating or preventing SARS-CoV-2 infection, with a particular focus on natural compounds present in food plants. Although some of the food plant secondary metabolites seem to be useful in the prevention and as a possible therapeutic management against SARS-CoV-2, up to now, no molecules can be used as a potential treatment for COVID-19; however, more research is needed.

Drug repurposing requires distinguishing established drug class targets from novel molecule-specific mechanisms and rapidly derisking their therapeutic potential in a time-critical manner, particularly in a pandemic scenario. In response to the challenge to rapidly identify treatment options for COVID-19, several studies reported that statins, as a drug class, reduce mortality in these patients. However, it is unknown if different statins exhibit consistent function or may have varying therapeutic benefit. A Bayesian network tool was used to predict drugs that shift the host transcriptomic response to SARS-CoV-2 infection towards a healthy state. Drugs were predicted using 14 RNA-sequencing datasets from 72 autopsy tissues and 465 COVID-19 patient samples or from cultured human cells and organoids infected with SARS-CoV-2. Top drug predictions included statins, which were then assessed using electronic medical records containing over 4,000 COVID-19 patients on statins to determine mortality risk in patients prescribed specific statins versus untreated matched controls. The same drugs were tested in Vero E6 cells infected with SARS-CoV-2 and human endothelial cells infected with a related OC43 coronavirus. Simvastatin was among the most highly predicted compounds (14/14 datasets) and five other statins, including atorvastatin, were predicted to be active in > 50% of analyses. Analysis of the clinical database revealed that reduced mortality risk was only observed in COVID-19 patients prescribed a subset of statins, including simvastatin and atorvastatin. In vitro testing of SARS-CoV-2 infected cells revealed simvastatin to be a potent direct inhibitor whereas most other statins were less effective. Simvastatin also inhibited OC43 infection and reduced cytokine production in endothelial cells. Statins may differ in their ability to sustain the lives of COVID-19 patients despite having a shared drug target and lipid-modifying mechanism of action. These findings highlight the value of target-agnostic drug prediction coupled with patient databases to identify and clinically evaluate non-obvious mechanisms and derisk and accelerate drug repurposing opportunities.