The outbreak of SARS-CoV-2 in December 2019 in China subsequently lead to a pandemic. Lack of vaccine and specific anti-viral drugs started a global health disaster. For a sustained control and protection, development of potential anti-viral drugs is one of the targeted approach. Although, designing and developing a panel of new drugs molecules are always encouraged. However, in the current emergency, drug repurposing study is one of the most effective and fast track option. The crystal structure of a SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2) RNA Dependent RNA Polymerase (RdRp) has recently been deciphered through X-ray crystallography. The single-chain of core RNA Dependent RNA Polymerase relies on virus-encoded cofactors nsp7 and two units of nsp8 for its optimum function. This study explored the FDA approved database of 7922 molecules and screened against the core polymerase along with cofactors. Here we report a panel of FDA approved drugs that show substantial interactions with key amino acid residues of the active site. Interestingly, some of the identified drugs (Ornipressin, Lypressin, Examorelin, Polymyxin B1) bind strongly within the binding pockets of both forms of RdRp. Besides, we found strong candidates for the complex form as well which include Nacortocin, Cistinexine, Cisatracurium (among others). These drugs have the potential to be considered while contriving therapeutic options.
Ethnomedicinal knowledge of plant-derived bioactives could help us in discovering new therapeutic compounds of great potential. Certainly, dandelion has been used in traditional ethno-medicinal systems (i.e., Chinese, Arabian, Indian, and Native American) to treat different types of cancer. Though, dandelion is highly vigorous, but the potential mode of action is still unclear. In the current study, the antiproliferative activity of methanolic extracts of dandelion root (MEDr) on cell viability of HepG2, MCF7, HCT116, and normal Hs27 was investigated. It was observed that MEDr (500 μg/mL) drastically decreased the growth of HepG2 cell line, while the effect on MCF7 and HCT116 cell lines was less pronounced and no effect has been observed in Hs27 cell lines. The MEDr also enhanced the phosphorylation level of AMPK of HepG2 cells, which considered crucial in cancer treatment and other metabolic diseases. The AMPK activation by MEDr noticed in the current study has never been reported previously. The results regarding the number of apoptotic cells (HepG2 cells) were in line with the cell viability test. The current observations clearly demonstrated the potency of MEDr against liver cancer with validation that dandelion could control AMPK and thus cancer in the treated cell lines.
Hepatitis C virus (HCV) leads to liver cirrhosis and carcinoma worldwide. The data of HCV cirrhotic patients were collected from hospitals of Peshawar in the period from 2015 to 2018. A total sample of 267 patients, in the age limit (>19 and <87 years) were found to be cirrhotic and HCV positive. The samples were analyzed through different tests, that is, raised alkaline phosphatase (410 IU/L), aspartate aminotransferase (209 U/L), and reverse transcription-polymerase chain reaction (PCR) viral load (>5,000,000 IU/mL). The mean and standard deviation (SD) of alanine transaminase and alpha fetoprotein were noted, (121.46 -29.23) and (43.09 -28.08), respectively. Samples of HCV cirrhotic patients (59.6% males and 40.4% females) were included and their mean age and SD of the patients was 49.62 -12.65 years. The Child-Turcotte-Pugh Score system was assessed on the base of liver disease. High blood pressure was observed in 26.2%, low in 40.8%, and normal in 33% of patients. The ascites was recorded high in 59% patients (male 38.6%, female 20.6%) and the level of albumin was abnormal in 64.5% patients. Furthermore, multiplex PCR was run to determine HCV genotypes. The frequency of HCV genotype 3a was 47.9%, 2a and 3b was 11%, 1a was 6%, and 1b was 1%; 4.1% were mixed genotypes and 18.7% were untypable genotypes in these patients. The HCV genotype 3a was found a major prevalent genotype in Khyber Pakhtunkhwa patients and it was observed that the HCV cirrhosis issue was significantly increased in the province.
In the quest for bioactive natural products of fungal origin, Aspergillus flavus was isolated from rhizosphere of Mentha piperita using Potato Dextrose Agar (PDA) and Czapec Yeast Broth (CYB) nutrient media for metabolites production. In total, three different metabolites were purified using HPLC/LCMS and the structures were established using 500 Varian NMR experiments. Further the isolated metabolites in different concentrations (10, 100, 1000 μg/mL) were tested for herbicidal activity using Completely Randomized design (CRD) against the seeds of Silybum marianum and Avena fatua which are major threats to wheat crop in Pakistan. Among the isolated metabolites, one compound was found active against the test weed species whose activity is reported in the present work. The chemical name of the compound is 2-(1, 4-dihydroxybutan-2-yl)-1, 3-dihydroxy-6, 8-dimethoxyanthracene-9, 10(4aH, 9aH)-dione with mass of 388. Results showed that all seeds germinated in control treatment; however, with the metabolite treated, the growth was retarded to different levels in all parts of the weeds. At a dose of 1000 μg/mL of the pure compound, 100% seeds of S. marianum and 60% seeds of A. fatua were inhibited. Interestingly, the pure compound exhibited less inhibition of 10% towards the seeds of common wheat (Triticum aestivum).
Hepatitis C virus (HCV), a small, single-stranded RNA virus with a 9.6 kb genome, is one of the most common causes of liver diseases. Sequencing of the 5ʹ untranslated region (UTR) is usually used for HCV genotyping, but it is less important in numerous subtypes due to its scarce sequence variations. This study aimed to identify genotypes using the 5ʹ UTR of HCV from cirrhotic patients of Khyber Pakhtunkhwa (KP). Serum RNA samples (44) were screened by real time PCR to determine the HCV viral load. Nested PCR was performed to identify cDNA and the 5ʹ UTR. The HCV 5′ UTR was sequenced using the Sanger method. MEGA-7 software was used to analyze evolutionary relatedness. After 5ʹ UTR sequencing, 26 samples (59%) were identified as genotype 3, and 2 samples (6%) were identified as genotypes 1, 2 and 4. The most predominant genotype was 3a, and genotype 4 was rarely reported in the phylogenetic tree. Analysis of the HCV 5ʹ UTR is an efficient alternative method for confirmation of various genotypes. Phylogenetic analysis showed that genotype 3 was dominant in the area of KP, Pakistan.
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