Cheminformatics and systems pharmacology approaches to unveil the potential plant bioactives to combat COVID-19.

COVID-19 was a global pandemic in the year 2020. Several treatment options failed to cure the disease. Thus, plant-based medicines are becoming a trend nowadays due to their less side effects. Bioactive chemicals from natural sources have been utilised for centuries as treatment options for a variety of ailments. To find out the potent bioactive compounds to counteract COVID-19, we use systems pharmacology and cheminformatics. They use the definitive data and predict the possible outcomes. In this study, we collected a total of 72 phytocompounds from the medicinally important plants such as Garcinia mangostana and Cinnamomum verum, of which 13 potential phytocompounds were identified to be active against the COVID-19 infection based on Swiss Target Prediction and compound target network analysis. These phytocompounds were annotated to identify the specific human receptor that targets COVID-19-specific genes such as MAPK8, MAPK14, ACE, CYP3A4, TLR4 and TYK2. Among these, compounds such as smeathxanthone A, demethylcalabaxanthone, mangostanol, trapezifolixanthone from Garcinia mangostana and camphene from C. verum were putatively target various COVID-19-related genes. Molecular docking results showed that smeathxanthone A and demethylcalabaxanthone exhibit increased binding efficiency towards the COVID-19-related receptor proteins. These compounds also showed efficient putative pharmacoactive properties than the commercial drugs ((R)-remdesivir, favipiravir and hydroxychloroquine) used to cure COVID-19. In conclusion, our study highlights the use of cheminformatics approach to unravel the potent and novel phytocompounds against COVID-19. These phytocompounds may be safer to use, more efficient and less harmful. This study highlights the value of natural products in the search for new drugs and identifies candidates with great promise.

[On indirect actions of Chinese medicines and innovation of indirect-acting Chinese medicines].

The output of high level innovative Chinese medicines(CM) is very rare for a few years, which is in sharp contrast to the reality that antibody drugs, small molecular targeted therapy, antibody-drug conjugate and other innovative drugs have heavy investment and high yield. Acceleration for the research and development of innovative CM drugs obviously relies on breakthrough of the modes of thinking and methodology. Deeply influenced by the thinking of allopathic medicine in Western science system, the mainstream of current basic researches on CM is to find the components and their molecular mechanisms that can directly inhibit or antagonize the target in disease focal. However, it is difficult to explain the mechanism of the reported " active" components in many CMs, since their steady-state concentrations in disease focal are usually significantly lower than the effective concentrations of those components. Therefore, based on the original methodology of CM-systemism and harmonizing medicine, this paper proposed that the mechanism of action of CMs may not be limited to the direct antagonistic effect on the target in disease focal. Instead, it may involve indirect action through the intermediate substances across different organs or systems with a long-distance action pattern.A fundamentally break may be achieved when exploring the mechanism of action of CM active components from the perspective of indirect action. It may also change the thinking of allopathic medicine in the researches of CM and start a new innovative road for the development of indirect-acting CMs.

Application of carbohydrates in approved small molecule drugs: A review.

Carbohydrates are an important energy source and play numerous key roles in all living organisms. Carbohydrates chemistry involved in diagnosis and treatment of diseases has been attracting increasing attention. Carbohydrates could be one of the major focuses of new drug discovery. Currently, however, carbohydrate-containing drugs account for only a small percentage of all drugs in clinical use, which does not match the important roles of carbohydrates in the organism. In other words, carbohydrates are a relatively untapped source of new drugs and therefore may offer exciting novel therapeutic opportunities. Here, we presented an overview of the application of carbohydrates in approved small molecule drugs and emphasized and evaluated the roles of carbohydrates in those drugs. The potential development direction of carbohydrate-containing drugs was presented after summarizing the advantages and challenges of carbohydrates in the development of new drugs.

On indirect actions of Chinese medicines and innovation of indirect-acting Chinese medicines / 中国中药杂志

The output of high level innovative Chinese medicines(CM) is very rare for a few years, which is in sharp contrast to the reality that antibody drugs, small molecular targeted therapy, antibody-drug conjugate and other innovative drugs have heavy investment and high yield. Acceleration for the research and development of innovative CM drugs obviously relies on breakthrough of the modes of thinking and methodology. Deeply influenced by the thinking of allopathic medicine in Western science system, the mainstream of current basic researches on CM is to find the components and their molecular mechanisms that can directly inhibit or antagonize the target in disease focal. However, it is difficult to explain the mechanism of the reported " active" components in many CMs, since their steady-state concentrations in disease focal are usually significantly lower than the effective concentrations of those components. Therefore, based on the original methodology of CM-systemism and harmonizing medicine, this paper proposed that the mechanism of action of CMs may not be limited to the direct antagonistic effect on the target in disease focal. Instead, it may involve indirect action through the intermediate substances across different organs or systems with a long-distance action pattern.A fundamentally break may be achieved when exploring the mechanism of action of CM active components from the perspective of indirect action. It may also change the thinking of allopathic medicine in the researches of CM and start a new innovative road for the development of indirect-acting CMs.

Novel Pharmacotherapy for Hypertrophic Cardiomyopathy.

Medical therapy for hypertrophic cardiomyopathy (HCM) has focused on minimizing the impact of symptoms due to left ventricular outflow tract obstruction and diastolic dysfunction. This article briefly discusses currently available therapy and focuses on both clinically available medications with novel applications for HCM as well as novel medications under development with specific indication for HCM. Finally, a brief summary of the current gaps and potential targets for pharmacotherapy is discussed.

Innovative solutions to novel drug development in mental health.

There are many new advances in neuroscience and mental health which should lead to a greater understanding of the neurobiological dysfunction in neuropsychiatric disorders and new developments for early, effective treatments. To do this, a biomarker approach combining genetic, neuroimaging, cognitive and other biological measures is needed. The aim of this article is to highlight novel approaches for pharmacological and non-pharmacological treatment development. This article suggests approaches that can be taken in the future including novel mechanisms with preliminary clinical validation to provide a toolbox for mechanistic studies and also examples of translation and back-translation. The review also emphasizes the need for clinician-scientists to be trained in a novel way in order to equip them with the conceptual and experimental techniques required, and emphasizes the need for private-public partnership and pre-competitive knowledge exchange. This should lead the way for important new holistic treatment developments to improve cognition, functional outcome and well-being of people with neuropsychiatric disorders.

Biotechnology in modernization of Chinese materia medica / 中草药

Chinese materia medica (CMM) plays an important role both in the disease prevention and therapy system and also in natural drug screening. Biotechnology exhibits applicable prospects in modern research of CMM with progress of natural science and technologies. Amplification fragment length polymorphism (AFLP), restriction fragment length polymorphism (RFLP), random amplification polymorphism of DNA (RAPD), and microsatellite DNA have been used to discriminate and breed herbal varieties. Genetic transformation and techniques of tissue and cell culture are explored to protect herbal resouces and to produce active components or parts on a commercial scale. High throughput technologies of proteome and biochip are expected to probe molecular targets and routes of CMM with the changes of proteome and gene expression. The results can be helpful to novel drug development and secondary exploitation, so as to promote the modernization process of CMM.