Day: December 5, 2020

Natural product-derived phytochemicals as potential agents against coronaviruses: A review

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Coronaviruses are responsible for a growing economic, social and mortality burden, as the causative agent of diseases such as severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), avian infectious bronchitis virus (IBV) and COVID-19. However, there is a lack of effective antiviral agents for many coronavirus strains. Naturally existing compounds provide a wealth of chemical diversity, including antiviral activity, and thus may have utility as therapeutic agents against coronaviral infections. The PubMed database was searched for papers including the keywords coronavirus, SARS or MERS, as well as traditional medicine, herbal, remedy or plants, with 55 primary research articles identified. The overwhelming majority of publications focussed on polar compounds. Compounds that show promise for the inhibition of coronavirus in humans include scutellarein, silvestrol, tryptanthrin, saikosaponin B2, quercetin, myricetin, caffeic acid, psoralidin, isobavachalcone, and lectins such as griffithsin. Other compounds such as lycorine may be suitable if a therapeutic level of antiviral activity can be achieved without exceeding toxic plasma concentrations. It was noted that the most promising small molecules identified as coronavirus inhibitors contained a conjugated fused ring structure with the majority being classified as being polyphenols.

Coronaviruses (CoVs) belong to the family Coronaviridae, subfamily Coronavirinae and are large (genome size 26−32 kb; Wu et al., 2020a), enveloped, positive-sense single-stranded ribonucleic acid (RNA) viruses that can infect both animals and humans. Based on their genotypic and serological characteristics, the viruses are subdivided into four genera: Alpha-, Beta-, Gamma-, and Deltacoronavirus (Chu et al., 2020; Lu et al., 2015). At present, all identified CoVs that are capable of infecting humans belong to the first two genera. These include the alphacoronaviruses (αCoVs) HCoV-NL63 (Human CoV-NL63) and HCoV-229E and the betacoronaviruses (βCoVs) HCoV-OC43 (Human CoV-OC43), HKU1 (Human CoV), SARS-CoV (Severe Acute Respiratory Syndrome CoV), and MERS-CoV (Middle Eastern Respiratory Syndrome CoV) (Lu et al., 2015). In the past two decades there have been three epidemics caused by the betaCoVs, namely SARS in 2002−03, MERS in 2012 and COVID-19, first identified in 2019. (Virus Res. 2020 Jul 15;284:197989. )

A Novel Antimicrobial-Phytochemical Conjugate With Antimicrobial Activity Against Streptococcus uberis, Enterococcus faecium, and Enterococcus faecalis

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Antimicrobial resistance is one of the major threats to human and animal health. An effective strategy to reduce and/or delay antimicrobial resistance is to use combination therapies. Research in our laboratory has been focused on combination therapies of antimicrobials and phytochemicals and development of antimicrobial-phytochemical conjugates. In this study, we report the synthesis and antimicrobial activity of a novel sulfamethoxazole-gallic acid conjugate compound (Hybrid 1). Hybrid 1 not only showed much stronger activity than sulfamethoxazole towards Streptococcus uberis 19436, Enterococcus faecium 700221, and Enterococcus faecalis 29212, which were purchased from American Type Culture Collection (ATCC), but also exhibited a promising antimicrobial effect against two E. faecalis clinical isolates, one of which was multidrug-resistant. Further studies are warranted to establish the in vivo antimicrobial activity for Hybrid 1 and develop more potent sulfamethoxazole-gallic acid-based antimicrobial conjugates using hybrid 1 as a lead compound. (Front Pharmacol. 2019 Nov 28;10:1405.)

A Phytochemical-Based Copolymer Derived from Coriolus versicolor Polysaccharopeptides for Gene Delivery

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Coriolus versicolor is an herb widely used for cancer treatment in traditional Chinese medicine. Its active ingredients, polysaccharopeptides (PSP), have been used for adjuvant therapies in cancer treatment. This study conjugates Coriolus versicolor PSP with poly(ethylenimine) (PEI) to generate a PSP-PEI copolymer for gene transfer. After PEI conjugation, both the pH buffering capacity and DNA compaction ability of PSP are significantly increased. Compared with that of PSP, the transfection efficiency of PSP-PEI is 10 to 20-fold higher in vitro. This is a proof-of-concept study reporting the direct use of bioactive phytochemicals from traditional Chinese medicine for gene vector development. The promising performance of PSP-PEI raises the possibility that bioactive herbal ingredients can be further developed as a multi-therapeutic gene carrier for tackling cancers.

C. versicolor PSP are water-soluble substances having a dark brown colour and characteristic odour. Their polysaccharide moieties are highly complex, consisting of glucose molecules linked with different sugar units (e.g., galactose, mannose, arabinose, and xylose); whereas the peptide moieties contain a large amount of aspartic acid and glutamic acid, with acidic and neutral amino acids (such as leucine, glycine, alanine, threonine, serine, glutamic acid, valine and aspartic acid) accounting for 70% of all kinds of amino acids present. PEI is a cationic aziridine polymer that exists as a polycation showing high pH buffering capacity over a broad range of pH values. Previous studies have revealed that the transfection efficiency and cytotoxicity of PEI are positively related to the molecular weight of PEI. As the aim of PEI incorporation in this study is to enhance the positive charge density of PSP, LMW PEI (e.g., PEI 0.8K) is adopted because it can serve the purpose and is less toxic than its high-molecular-weight counterparts. During synthesis, 1,1′-carbonyldiimidazole (CDI), which activates the hydroxyl groups of PSP to form active imidazolyl carbamate intermediates, is used as a coupling agent. The intermediates are subsequently attacked by the primary amine groups of PEI to form PSP-PEI, with imidazole being released as a byproduct. (Molecules. 2018 Sep 6;23(9):2273.)