Dihydroartemisinin for COVID-19

The advantages of a treatment modality that combines two or more therapeutic agents with different mechanisms of action encourage the study of hybrid functional compounds for pharmacological applications. Molecular hybridization, resulting from a covalent combination of two or more pharmacophore units, has emerged as a promising approach to overcome several issues and has also been explored for the design of new drugs for COVID-19 treatment. In this review, we presented an overview of small-molecule hybrids from both natural products and synthetic sources reported in the literature to date with potential antiviral anti-SARS-CoV-2 activity.

The COVID-19 pandemic has posed a significant threat to society in recent times, endangering human health, life, and economic well-being. The disease spreads quickly due to the highly infectious SARS-CoV-2 virus, which has undergone numerous mutations. Despite intense research efforts by the scientific community since its emergence in 2019, no effective therapeutics have been discovered yet. While some repurposed drugs have been used to control the global outbreak and save lives, none have proven universally effective, particularly for severely infected patients. Although the spread of the disease is generally under control, anti-SARS-CoV-2 agents are still needed to combat current and future infections. This study reviews some of the most promising repurposed drugs containing indolyl heterocycle, which is an essential scaffold of many alkaloids with diverse bio-properties in various biological fields. The study also discusses natural and synthetic indole-containing compounds with anti-SARS-CoV-2 properties, as well as computer-aided drug design (in-silico studies) for optimizing anti-SARS-CoV-2 hits/leads.

IntroductionThe COVID-19 Disease Map project is a large-scale community effort uniting 277 scientists from 130 Institutions around the globe. We use high-quality, mechanistic content describing SARS-CoV-2-host interactions and develop interoperable bioinformatic pipelines for novel target identification and drug repurposing. MethodsExtensive community work allowed an impressive step forward in building interfaces between Systems Biology tools and platforms. Our framework can link biomolecules from omics data analysis and computational modelling to dysregulated pathways in a cell-, tissue- or patient-specific manner. Drug repurposing using text mining and AI-assisted analysis identified potential drugs, chemicals and microRNAs that could target the identified key factors.ResultsResults revealed drugs already tested for anti-COVID-19 efficacy, providing a mechanistic context for their mode of action, and drugs already in clinical trials for treating other diseases, never tested against COVID-19. DiscussionThe key advance is that the proposed framework is versatile and expandable, offering a significant upgrade in the arsenal for virus-host interactions and other complex pathologies.

The outbreak of the new coronavirus (COVID-19) has been transferred exponentially. There are many articles that have found the inhibitory effect of plant extracts or plant compounds on the coronavirus family. In this study, we want to use systematic review and meta-analysis to answer the question of which herbal compound can be more effective against the coronavirus. The present study is based on the guidelines for conducting meta-analyzes. An extensive search was conducted in the electronic database, and based on the inclusion and exclusion criteria, articles were selected and data screening was performed. Quality control of articles was performed. Data analysis was carried out in STATA software. The results showed that alkaloid compounds had a good effect in controlling the coronavirus and reducing viral titer. Trypthantrin, Sambucus extract, S. cusia extract, Boceprevir and Indigole B, dioica agglutinin urtica had a good effect on reducing the virus titer but their selectivity index has not been reported and it is recommended to determine for these compounds. Also among the compounds that had the greatest effect on virus inhibition, including Saikosaponins B2, SaikosaponinsD, SaikosaponinsA and Phillyrin, had an acceptable selectivity index greater than 10. Andrographolide showed the highest selectivity index on SARS-COV2, while virus titration and virus inhibition were not reported. The small number of studies that used alkaloid compounds was one of the limitations and it is suggested to investigate the effect of more alkaloid compounds against the coronavirus for verifying its effect.