Comparative inhibition analysis of wild type and G671S catalytic site mutant of the SARS-CoV-2 RNA-dependent RNA polymerase

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) has wrecked a global havoc, after its emergence in Wuhan, Hubei province of China. It is known to have a distressing effect on the respiratory tract and has a high mortality rate. Till to date (25 Dec 2021), total number of cases (279,362,428) have been reported across the globe. Variable mutations have been reported on various geographical levels. In this study, we have analyzed G671S mutation of RdRp of the SARS-CoV-2, which has been reported in various strains globally, but importantly delta variant cases of Pakistan and has a serious impact on the protein structure. To study the conformational impact, we screened a Tibetan medicinal compound/Sowa Rigpa library against RdRp and compared the best docked compound (Kaempferol 3-O-gentiobioside) to the wild type and mutant RdRp against Remdesivir. A short simulation was used to validate the findings. Both remdesivir and our screened compound showed better inhibition for mutant, compared to the wild type RdRp.

KAJIAN LITERATUR DAN KROMATOGRAFI UNTUK HERBA KESUM

<p align="center"><strong>ABSTRAK</strong></p><p> </p><p>Spesis <em>Polygonum</em> (misalnya <em>P. aviculare</em>) dilaporkan mempunyai kandungan alkaloid. Begitu juga dengan daun kesum (<em>P. minus</em> Huds), yang terbukti sebagai sumber molekul perubatan semulajadi. Masalah yang diidentifikasi dari kajian kesum termasuklah di dalam aspek fitokimia genus <em>Polygonum</em> ini, yang belum pernah disiasat secara mendalam. Oleh itu, sasaran kajian ini adalah untuk mengulas data biokimia tumbuhan tersebut melalui metode literatur serta menjalankan telaah analisis kimia terhadap ekstrak kesum. Dari artikel dan jurnal penerbitan, bahagian daun dan akar dipelajari melalui kaedah kromatografi kolom. Tambahan itu, sebatian kimia dari kesum dicirikan dengan teknik spektroskopi resonans magnetik nuklear. Temuan signifikan diperolehi apabila senyawa indol dan alkaloid diterpen C20 berjaya dikarakterisasi. Secara kesimpulannya, projek di masa hadapan boleh ditumpu kepada ujikaji antikanser dan anti-penuaan dari herba kesum ini. </p><p> </p><p><strong>Kata kunci</strong> : herba, kesum, literatur, <em>Polygonum</em></p><p> </p><p align="center"><strong><em>ABSTRACT</em></strong></p><p> </p><p><em>Polygonum species (e.g. P. aviculare) were reported to consist of alkaloidal nature. Likewise, the kesum leaves (P. minus Huds) is </em><em>proven as a source of natural medicinal compound. </em><em>The identified problem in the kesum research would include the phytochemistry </em><em>aspects of this Polygonum </em><em>genus, which is not yet thoroughly investigated</em><em>, via literature search. </em><em>Therefore, the aim of this study is to accumulate </em><em>and review the biochemical data of this herb. </em><em>From the articles and published journals, the leaves and root extracts</em><em> were analysed by using liquid chromatographic </em><em>technique. In addition, the chemical substance from kesum could be elucidated via nuclear magnetic resonance spectroscop</em><em>y. The </em><em>significant findings could be obtained when the indole and and C20-diterpene alkaloids</em><em> were successfully characterised. In summary, future directions of the project </em><em>could </em><em>focus on anticancer</em><em> and anti-aging experiments of this kesum herb. </em></p><p> </p><p><strong><em>Keywords</em></strong><em> : herb, kesum, literatur</em><em>e, Polygonum </em></p>

An overview of the anti-cancer actions of Tanshinones, derived from Salvia miltiorrhiza (Danshen)

Tanshinone is a herbal medicinal compound described in Chinese medicine, extracted from the roots of Salvia miltiorrhiza (Danshen). This family of compounds, including Tanshinone IIA and Tanshinone I, have shown remarkable potential as anti-cancer molecules, especially against breast, cervical, colorectal, gastric, lung, and prostate cancer cell lines, as well as leukaemia, melanoma, and hepatocellular carcinoma among others. Recent data has indicated that Tanshinones can modulate multiple molecular pathways such as PI3K/Akt, MAPK and JAK/STAT3, and exert their pharmacological effects against different malignancies. In addition, preclinical and clinical data, together with the safety profile of Tanshinones, encourage further applications of these compounds in cancer therapeutics. In this review article, the effect of Tanshinones on different cancers, challenges in their pharmacological development, and opportunities to harness their clinical potential have been documented.

The design optimization of Chinese medicinal compound for the treatment of co-infection of Mycoplasma gallisepticum and Escherichia Coli

Background: A new Chinese medicinal compound including Isatdis Radix, Forsythiae Fructus, Mori Cortex, Ginkgo Folium, Licorice and Radix Salviae was pre-screened through the method of network pharmacology for the treatment of co-infection of Mycoplasma gallisepticum and Escherichia Coli. While, the optimal combination of Chinese medicine is still an obstacle to the development of the Chinese medicinal compound.Results: A multi-indicators evaluation method was used in this study to establish a comprehensive assessment system based on the minimal inhibitory concentration of Mycoplasma gallisepticum and Escherichia Coli in vitro, air sac and tracheal lesion scores in vivo. We used the min-max normalization method to normalize the scores of the four metrics and gave them the same proportion of weights to calculate the total score. Then, according to the method of uniform test, the six-factor ten-level experiment (U*10(106) was designed, with the total score as the index. The multi-nonlinear regression equation was established by data processing system according to the comprehensive index. The results showed that the ratio of Isatdis Radix, Forsythiae Fructus, Ginkgo Folium, Mori Cortex, Licorice and Radix Salviae were 14:7:11:12:5:3, which showed effective treatment. Conclusions: It turned out that uniform design can be effectively used to solve dose optimization for combined use of multiple compounds. In addition, this study also proposes a new method to comprehensively evaluate medicinal compounds for respiratory diseases such as Mycoplasma gallisepticum and Escherichia Coli infection.

Cucurbitacins and its Anticancer property: A Review

Cucurbitacins which are structurally unlike triterpenes found in the members of Cucurbitaceae and several other plant families possess immense pharmacological activity. This diverse group of compounds may substantiate to be important lead molecules for the treatment of cancer. Research focused on this unattended medicinal compound can prove the significance and explore the hidden potential to cure various diseases. These compounds show their proposed mode of action, probable molecular targets and have future aspects of their use as a medicinal agent. This review is aimed to provide the chemical nature and medicinal property of cucurbitacins.

Quercetin is a Useful Medicinal Compound Showing Various Actions Including Control of Blood Pressure, Neurite Elongation and Epithelial Ion Transport

Quercetin has multiple potential to control various cell function keeping our body condition healthy. In this review article, we describe the molecular mechanism on how quercetin exerts its action on blood pressure, neurite elongation and epithelial ion transport based from a viewpoint of cytosolic Cl- environments, which is recently recognized as an important signaling factor in various types of cells. Recent studies show various roles of cytosolic Cl- in regulation of blood pressure and neurite elongation, and prevention from bacterial and viral infection. We have found the stimulatory action of quercetin on Cl- transporter, Na+-K+-2Cl- cotransporter 1 (NKCC1; an isoform of NKCC), which has been recognized as one of the most interesting, fundamental actions of quercetin. In this review article, based on this stimulatory action of quercetin on NKCC1, we introduce the molecular mechanism of quercetin on: 1) blood pressure, 2) neurite elongation, and 3) epithelial Cl- secretion including tight junction forming in epithelial tissues. 1) Quercetin induces elevation of the cytosolic Cl- concentration via activation of NKCC1, leading to anti-hypertensive action by diminishing expression of epithelial Na+ channel (ENaC), a key ion channel involved in renal Na+ reabsorption, while quercetin has no effects on the blood pressure with normal salt intake. 2) Quercetin also has stimulatory effects on neurite elongation by elevating the cytosolic Cl- concentration via activation of NKCC1 due to tubulin polymerization facilitated through Cl--induced inhibition of GTPase. 3) Further, in lung airway epithelia quercetin stimulates Cl- secretion by increasing the driving force for Cl- secretion via elevation of the cytosolic Cl- concentration: this leads to water secretion, participating in prevention of our body from bacterial and viral infection. In addition to transcellular ion transport, quercetin regulates tight junction function via enhancement of tight junction integrity by modulating expression and assembling tight junction-forming proteins. Based on these observations, it is concluded that quercetin is a useful medicinal compound keeping our body to be in healthy condition.