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The widespread nature of several viruses is greatly credited to their rapidly altering RNA genomes that enable the infection to persist despite challenges presented by host cells. Within the RNA genome of infections is RNA-dependent RNA polymerase (RdRp), which is an essential enzyme that helps in RNA synthesis by catalysing the RNA template-dependent development of phosphodiester bonds. Therefore, RdRp is an important therapeutic target in RNA virus-caused diseases, including SARS-CoV-2. In this review, we describe the promising RdRp inhibitors that have been launched or are currently in clinical studies for the treatment of RNA virus infections. Structurally, nucleoside inhibitors (NIs) bind to the RdRp protein at the enzyme active site, and nonnucleoside inhibitors (NNIs) bind to the RdRp protein at allosteric sites. By reviewing these inhibitors, more precise guidelines for the development of more promising anti-RNA virus drugs should be set, and due to the current health emergency, they will eventually be used for COVID-19 treatment., Graphical abstract Image 1, Highlights • This article provides an overview of RdRp inhibitors that have been launched or are in clinical studies for the treatment of RNA virus infections, including COVID-19. • Nucleoside inhibitors (NIs) exhibit broad-spectrum antiviral activity but pose a more serious toxicity risk than non-nucleoside inhibitors (NNIs) because high dosages of NIs result in accumulation in plasma. • Structurally diverse NNIs are endowed with high potential activities but tend to induce drug resistance due to the RdRp allosteric site.

Bruton's tyrosine kinase (BTK) has emerged as a promising drug target for multiple diseases, particularly haematopoietic malignancies and autoimmune diseases related to B lymphocytes. This review focuses on the diverse, small-molecule inhibitors of BTK kinase that have shown good prospects for clinical application. Individual examples of these inhibitors, including both reversible and irreversible inhibitors and a recently developed reversible covalent inhibitor of BTK, are discussed. Considerable progress has been made in the development of irreversible inhibitors, most of which target the SH3 pocket and the cysteine 481 residue of BTK. The present review also surveys the pharmacological advantages and deficiencies of both reversible and irreversible BTK drugs, with a focus on the structure-activity relationship (SARs) and binding modes of representative drugs, which could inspire critical thinking and new ideas for developing potent BTK inhibitors with less unwanted off-target effects.

Bioactive film from sturgeon skin gelatine incorporated with esculine at various concentrations (0.3%, 0.6% and 0.9% w/v) was developed. The physical, mechanical and antioxidant properties of esculine sturgeon gelatine biocomposite films were investigated. The results indicated that the incorporation of esculine into gelatine films significantly increased the DPPH (2,2-diphenyl-1-picrylhydrazyl) radical-scavenging activity and reducing power in a concentration-dependent manner (p 0.05). Water vapour permeability (WVP) and solubility of esculine-containing films decreased as the amount of esculine increased (p

Highlights • The present review summarizes the plausible molecular mechanism of specific LH capsules in the control of SARS-COV-2 infection and the inhibition of cytokine storms caused by IL-6. • Preclinical and clinical trials of LH capsules in COVID-19 conducted in and outside China are elaborated. • A promising antiviral mechanism of LH capsules is defined, and the mechanism involving the suppression of inflammatory cytokine storms is explained. • Active substances in LH capsules that dock in ACE2 to prevent S protein binding are highlighted., Background In December 2019, a novel coronavirus, SARS-CoV-2 caused a series of acute atypical respiratory diseases worldwide. However, there is still a lack of drugs with clear curative effects, and the clinical trial research of vaccines has not been completely finished. Purpose LH capsules are approved TCM patent medicine that are widely used for the treatment of respiratory tract infectious diseases caused by colds and flu. On April 12, 2020, LH capsules and granules were officially repurposed by the China Food and Drug Administration (CFDA) for patients with mild COVID-19 based on their safety and efficacy demonstrated through multicentre, randomized, controlled clinical trials. We hope to conduct a comprehensive review of it through modern pharmacy methods, and try to explain its possible mechanism. Methods Using the full names of LH capsules Lianhuaqingwen, Lianhua Qingwen andSARS-COV-2, COVID-19 as the keywords of the search terms, systemically search for existing related papers in various databases such as Web of Science and PubMed. And completed the collection of clinical data in ClinicalTrials.gov and Chinese Clinical Trial Registry. Last but not least, we have sorted out the anti-inflammatory and antiviral mechanisms of LH capsules through literature and Selleck. Results This review systematically sorted out the active ingredients in LH capsules. Furthermore, the related pharmacological and clinical trials of LH capsule on SARS-CoV-2, IAV and IBV were discussed in detail. Moreover, the present review provides the first summary of the potential molecular mechanism of specific substances in LH capsules involved in resistance to SARS-COV-2 infection and the inhibition of cytokine storm syndrome (CSS) caused by IL-6. Conclusion This review summarizes the available reports and evidence that support the use of LH capsules as potential drug candidates for the prevention and treatment of COVID-19. However, TCM exerts its effects through multiple targets and multiple pathways, and LH capsules are not an exception. Therefore, the relevant mechanisms need to be further improved and experimentally verified., Graphical abstract Image, graphical abstract

Fourteen bergenin/cinnamic acid hybrids were synthesized, characterized and evaluated for their antitumour activity both in vitro and in vivo. The most potent compound, 5c, arrested HepG2 cells (IC50 = 4.23 ± 0.79 μM) in the G2/M phase and induced cellular apoptosis. Moreover, compound 5c was also found to suppress the tumour growth in Heps xenograft-bearing mice with low toxicity. In the mechanistic study, 5c administration ignited a mitochondria-mediated apoptosis pathway of HepG2 cell death. Furthermore, 5c activated Akt-dependent pathways and further decreased the expression of the Bcl-2 family of proteins. The downstream mitochondrial p53 translocation was also significantly activated, accompanied by an increase of the caspase-9, caspase-3 activation. These data imply that bergenin/cinnamic acid hybrids could serve as novel Akt/Bcl-2 inhibitors for further preclinical studies.