Current Updates on Naturally Occurring Compounds Recognizing SARS-CoV-2 Druggable Targets

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been identified in China as the etiologic agent of the recent COVID-19 pandemic outbreak. Due to its high transmissibility, this virus quickly spread throughout the world, causing considerable health issues. The scientific community exerted noteworthy efforts to obtain therapeutic solutions for COVID-19, and new scientific networks were constituted. No certified drugs to efficiently inhibit the virus were identified, and the development of de-novo medicines requires approximately ten years of research. Therefore, the repurposing of natural products could be an effective strategy to handle SARS-CoV-2 infection. This review aims to update on current status of the natural occurring compounds recognizing SARS-CoV-2 druggable targets. Among the clinical trials actually recruited, some natural compounds are ongoing to examine their potential role to prevent and to treat the COVID-19 infection. Many natural scaffolds, including alkaloids, terpenes, flavonoids, and benzoquinones, were investigated by in-silico, in-vitro, and in-vivo approaches. Despite the large data set obtained by a computational approach, experimental evidences in most cases are not available. To fill this gap, further efforts to validate these results are required. We believe that an accurate investigation of naturally occurring compounds may provide insights for the potential treatment of COVID-19 patients.

Rutin Is a Low Micromolar Inhibitor of SARS-CoV-2 Main Protease 3CLpro: Implications for Drug Design of Quercetin Analogs

“…However, and despite the huge number of research studies reported so far, the development of safe and effective drugs able to block the viral infection is still lacking and represents a major goal for the scientific world. Among all the possible chemical compounds, particular attention has been dedicated to molecules of natural origin [5][6][7][8], including extracts, single bioactive molecules, or entire classes of phytochemicals targeting SARS-CoV-2, and several of them are currently under investigation.…”

Interference of Polydatin/Resveratrol in the ACE2:Spike Recognition during COVID-19 Infection. A Focus on Their Potential Mechanism of Action through Computational and Biochemical Assays

“…Drugs able to bind key regions of the selected targets with high affinity and specificity could in principle sterically block the binding sites of the viral/host proteins or induce conformational switches in the biomolecules avoiding their correct recognition. Various works have already investigated, experimentally or in silico, the effects of natural compounds or synthetic drugs on COVID-19-related targets [21][22][23][24][25]. Several natural products endowed with significant biological activities, especially extracted from plants, have been thus identified as potentially able to contrast the dissemination of Coronavirus and, at the same time, enhance immunity, stimulating further screenings to discover new candidate drugs.…”

Computational Simulations Identified Marine-Derived Natural Bioactive Compounds as Replication Inhibitors of SARS-CoV-2

“…Recently, several drugs including Lopinavir, Ritonavir, Remdesivir, and Favipiravir were repurposed and are currently under clinical trials to assess their anti-viral efficacy and safety for the treatment of COVID-19 (Drożdżal et al, 2020). Similarly, the recent study reviewed various natural compounds such as Artemisinin, Berbrine, Cholcgicine, Glycyrrhizin, Hanfangchin A, Lactoferrin, Quercetin, Resveratrol Vitamin C, and Vitamin D were found effective against SARS-CoV-2 druggable targets and are currently in clinical trials (Romeo et al, 2021). The previously mentioned study confirms that natural compounds can act as lead scaffolds for drug design or help in improving immunity.…”