The CLKs (Cdc2-like kinases) belong to the dual-specificity protein kinase family and play crucial roles in regulating transcript splicing via the phosphorylation of SR proteins (SRSF1-12), catalyzing spliceosome molecular machinery, and modulating the activities or expression of non-splicing proteins. The dysregulation of these processes is linked with various diseases, including neurodegenerative diseases, Duchenne muscular dystrophy, inflammatory diseases, viral replication, and cancer. Thus, CLKs have been considered as potential therapeutic targets, and significant efforts have been exerted to discover potent CLKs inhibitors. In particular, clinical trials aiming to assess the activities of the small molecules Lorecivivint on knee Osteoarthritis patients, and Cirtuvivint and Silmitasertib in different advanced tumors have been investigated for therapeutic usage. In this review, we comprehensively documented the structure and biological functions of CLKs in various human diseases and summarized the significance of related inhibitors in therapeutics. Our discussion highlights the most recent CLKs research, paving the way for the clinical treatment of various human diseases.

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To date, the leading causes of mortality and morbidity worldwide include viral infections, such as Ebola, influenza virus, acquired immunodeficiency syndrome (AIDS), severe acute respiratory syndrome (SARS) and recently COVID-19 disease, caused by the SARS-CoV-2 virus. Currently, we can count on a narrow range of antiviral drugs, especially older generation ones like ribavirin and interferon which are effective against viruses in vitro but can often be ineffective in patients. In addition to these, we have antiviral agents for the treatment of herpes virus, influenza virus, HIV and hepatitis virus. Recently, drugs used in the past especially against ebolavirus, such as remdesivir and favipiravir, have been considered for the treatment of COVID-19 disease. However, even if these drugs represent important tools against viral diseases, they are certainly not sufficient to defend us from the multitude of viruses present in the environment. This represents a huge problem, especially considering the unprecedented global threat due to the advancement of COVID-19, which represents a potential risk to the health and life of millions of people. The demand, therefore, for new and effective antiviral drugs is very high. This review focuses on three fundamental points: (1) presents the main threats to human health, reviewing the most widespread viral diseases in the world, thus describing the scenario caused by the disease in question each time and evaluating the specific therapeutic remedies currently available. (2) It comprehensively describes main phytochemical classes, in particular from plant foods, with proven antiviral activities, the viruses potentially treated with the described phytochemicals. (3) Consideration of the various applications of drug delivery systems in order to improve the bioavailability of these compounds or extracts. A PRISMA flow diagram was used for the inclusion of the works. Taking into consideration the recent dramatic events caused by COVID-19 pandemic, the cry of alarm that denounces critical need for new antiviral drugs is extremely strong. For these reasons, a continuous systematic exploration of plant foods and their phytochemicals is necessary for the development of new antiviral agents capable of saving lives and improving their well-being.

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The recent coronavirus disease 2019 (COVID-19) pandemic is a global threat for healthcare management and the economic system, and effective treatments against the pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus responsible for this disease have not yet progressed beyond the developmental phases. As drug refinement and vaccine progression require enormously broad investments of time, alternative strategies are urgently needed. In this study, we examined phytochemicals extracted from Avicennia officinalis and evaluated their potential effects against the main protease of SARS-CoV-2. The antioxidant activities of A. officinalis leaf and fruit extracts at 150 µg/mL were 95.97% and 92.48%, respectively. Furthermore, both extracts displayed low cytotoxicity levels against Artemia salina . The gas chromatography-mass spectroscopy analysis confirmed the identifies of 75 phytochemicals from both extracts, and four potent compounds, triacontane, hexacosane, methyl linoleate, and methyl palminoleate, had binding free energy values of -6.75, -6.7, -6.3, and -6.3 Kcal/mol, respectively, in complexes with the SARS-CoV-2 main protease. The active residues Cys145, Met165, Glu166, Gln189, and Arg188 in the main protease formed non-bonded interactions with the screened compounds. The root-mean-square difference (RMSD), root-mean-square fluctuations (RMSF), radius of gyration (Rg), solvent-accessible surface area (SASA), and hydrogen bond data from a molecular dynamics simulation study confirmed the docked complexes' binding rigidity in the atomistic simulated environment. However, this study's findings require in vitro and in vivo validation to ensure the possible inhibitory effects and pharmacological efficacy of the identified compounds.

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Medicinal plants have been widely used to treat a variety of infectious and non-infectious ailments. According to one estimate, 25% of the commonly used medicines contain compounds isolated from plants. Several plants could offer a rich reserve for drug discovery of infectious diseases, particularly in an era when the latest separation techniques are available on one hand, and the human population is challenged by a number of emerging infectious diseases on the other hand. Among several other ailments, viral infections, particularly infections associated with human immunodeficiency virus type 1 (HIV-1) and 2 (HIV-2), and newly emerging infectious viruses have challenged mankind survival. Of importance, a variety of medicinal plants have shown promise to treat a number of viral infections, and some of them possess broad-spectrum antiviral activity. In the past, exploration into the antiviral activity of various promising medicinal plants was limited due to: (a) highly infectious nature of viruses and (b) lack of appropriate separation techniques for the identification of antiviral components from plants. Development of vector-based strategies, in which non-infectious molecular clone of a virus could be used for antiviral screening purposes, and advancement in separation technologies offers promise for medicinal plants usage in modern drug discovery. This article describes potential antiviral properties of medicinal plants against a diverse group of viruses, and suggests screening the potential of plants possessing broad-spectrum antiviral effects against emerging viral infections.

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The aqueous extracts from 21 medicinal herbs traditionally used in southern mainland China were screened for antiviral activities against human herpes simplex virus type 1 (HSV-1) and human respiratory syncytial virus (RSV) using a cytopathic effect (CPE) reduction assay. Three extracts from Agrimonia pilosa, Pithecellobium clypearia and Punica granatum, respectively, showed anti-HSV-1 activity, which was possibly contributed by the polyphenolic compounds in the herbal extracts. Six of the extracts, from Blumea laciniata, Elephantopus scaber, Laggera pterodonta, Mussaenda pubescens, Schefflera octophylla and Scutellaria indica, respectively, exhibited anti-RSV activity with 50% inhibition (IC50) concentrations ranging from 12.5 to 32 microg/mL, and selective indices (SI) ranging from 11.2 to 40. In addition to polyphenolic compounds, other constituents present in these extracts may also contribute to their anti-RSV activity.

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