Latest progress in research on natural compounds derived from plants for HIV resistance
AIDS is an infectious disease caused by human immunodeficiency virus (HIV). As of 2020, there were approximately 37.7 million infected individuals worldwide, 1.5 million new infections, and 680000 deaths from HIV related diseases. The main steps of HIV infected host cells include adsorption, fusion, uncoating, reverse transcription, integration, DNA replication, transcription, protein translation, maturation, and budding. According to the replication cycle of HIV, anti HIV drugs are divided into nucleoside reverse transcriptase inhibitors (NRTIs), non nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), integrase inhibitors (INSTIs), and co receptor inhibitors. The US FDA has approved over 30 drugs that can effectively inhibit HIV replication, but there is still no complete cure for HIV. Currently, highly active antiretroviral therapy (HAART) is the most effective method for treating HIV infection, transforming it from a fatal disease to a controllable chronic disease. Although HAART therapy has achieved great success in controlling AIDS, its efficacy is also significantly reduced due to cross resistance, adverse reactions and poor patient compliance. Therefore, the research and development of new anti HIV drugs with higher antiviral effect, lower side effects and higher drug resistance barrier is still urgently needed for the current prevention and treatment of AIDS.

China has extremely abundant medicinal resources, and relevant surveys show that there are 12807 species of medicinal herbs in China, including 11146 species of medicinal plants, accounting for 87%; 1581 species of medicinal animals, accounting for 12%; 80 types of mineral drugs, less than 1%. Natural products play a crucial role in drug development in various fields such as cancer, infectious diseases, and cardiovascular diseases. Among the 371 drugs included in the 9th edition of the International Pharmacopoeia, over 80 are natural products or derivatives of natural products; According to literature records, 70% of the 1562 new drugs approved between 1981 and 2014 were natural products. The World Health Organization (WHO) statistics show that 65% of the world’s population still uses plants and herbs as part of disease treatment.

Researchers have conducted extensive research on the anti HIV effects of natural products and found that various medicinal plants such as rhubarb, sword leaf three treasure wood, green plum, brown algae, Vernonia, geranium, and spike flower have significant anti HIV activity. The targets of most natural products are integrase (IN), reverse transcriptase (RT), and protease, and some natural products also have latent activation functions. The natural compounds with anti HIV activity mainly include coumarins, terpenes, flavonoids, alkaloids, phenols, lignans, quinones, saponins, anthraquinone, polysaccharides, tannins, proteins, and peptides. This article provides a brief review of the research on natural products with anti HIV activity from plant sources in the past 5 years, based on the long-term anti HIV drug research in the author’s laboratory.

 

 

Lead compounds extracted from natural resources such as medicinal plants are still one of the choices for treating various infectious and non infectious diseases. After experiencing the golden age of 1950-1960, the development of natural product drugs was almost stagnant due to technologies such as biological activity testing and combinatorial chemistry. With the rapid development of synthetic biology in recent years, new opportunities have been brought to the research and development of natural product drugs, promoting the progress of natural product drug development. Since the first FDA approved oral plant-based drug, crofelemer, was launched in 2012, it has brought tremendous momentum to the development of drugs derived from natural products.

In recent years, scientists have extracted and isolated many new compounds from plants, but a considerable number of these compounds only have weak inhibitory effects on HIV virus and low therapeutic indices, which poses certain challenges for the development of anti HIV drugs from natural sources. Plant derived drugs have the characteristics of multi-target, multi link, and multi pathway effects, making their mechanism of action more complex. Until now, there are still many plant extracts whose targets have not been fully elucidated. We should objectively recognize the potential of compounds derived from natural products in HIV/AIDS treatment and fully leverage their advantages. Combining modern science and technology to modify the structure of effective compounds, in order to obtain compounds with better therapeutic effects. Although there is still a long way to go in achieving functional cure for HIV, we should fully utilize the advantages of natural products and explore the development of safe and effective therapeutic drugs.