Comparative expression analysis of sucrose phosphate synthase gene family in a low and high sucrose Pakistani sugarcane cultivars.

Sugarcane is the world's largest cultivated crop by biomass and is the main source of sugar and biofuel. Sucrose phosphate synthase (SPS) enzymes are directly involved in the synthesis of sucrose. Here, we analyzed and compared one of the important gene families involved in sucrose metabolism in a high and low sucrose sugarcane cultivar. A comprehensive in silico analysis of the SoSPS family displayed their phylogenetic relationship, gene and protein structure, miRNA targets, protein interaction network (PPI), gene ontology and collinearity. This was followed by a spatial expression analysis in two different sugarcane varieties. The phylogenetic reconstruction distributed AtSPS, ZmSPS, OsSPS, SoSPS and SbSPS into three main groups (A, B, C). The regulatory region of SoSPS genes carries ABRE, ARE, G-box, and MYC as the most dominant cis-regulatory elements. The PPI analysis predicted a total of 14 unique proteins interacting with SPS. The predominant expression of SPS in chloroplast clearly indicates that they are the most active in the organelle which is the hub of photosynthesis. Similarly, gene ontology attributed SPS to sucrose phosphate synthase and glucosyl transferase molecular functions, as well as sucrose biosynthetic and disaccharide biological processes. Overall, the expression of SPS in CPF252 (high sucrose variety) was higher in leaf and culm as compared to that of CPF 251 (low sucrose variety). In brief, this study adds to the present literature about sugarcane, sucrose metabolism and role of SPS in sucrose metabolism thereby opening up further avenues of research in crop improvement.

Computational Advancement towards the Identification of Natural Inhibitors for Dengue Virus: A Brief Review.

Viral infectious illnesses represent a severe hazard to human health due to their widespread incidence worldwide. Among these ailments, the dengue virus (DENV) infection stands out. World Health Organization (WHO) estimates that DENV infection affects ~400 million people each year, with potentially fatal symptoms showing up in 1% of the cases. In several instances, academic and pharmaceutical researchers have conducted several pilot and clinical studies on a variety of topics, including viral epidemiology, structure and function analyses, infection source and route, therapeutic targets, vaccinations, and therapeutic drugs. Amongst Takeda, TAK-003, Sanofi, Dengvaxia®, and Butantan/NIH/Merck, Dengvaxia® (CYD-TDV) is the only licensed vaccination yet; however, the potential inhibitors are under development. The biology and evolution of DENVs are briefly discussed in this review, which also compiles the most recent studies on prospective antiviral targets and antiviral candidates. In conclusion, the triumphs and failures have influenced the development of anti-DENV medications, and the findings in this review article will stimulate more investigation.

Mutational analysis of the spike protein of SARS-COV-2 isolates revealed atomistic features responsible for higher binding and infectivity.

Introduction: The perpetual appearance of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV-2), and its new variants devastated the public health and social fabric around the world. Understanding the genomic patterns and connecting them to phenotypic attributes is of great interest to devise a treatment strategy to control this pandemic. Materials and Methods: In this regard, computational methods to understand the evolution, dynamics and mutational spectrum of SARS-CoV-2 and its new variants are significantly important. Thus, herein, we used computational methods to screen the genomes of SARS-CoV-2 isolated from Pakistan and connect them to the phenotypic attributes of spike protein; we used stability-function correlation methods, protein-protein docking, and molecular dynamics simulation. Results: Using the Global initiative on sharing all influenza data (GISAID) a total of 21 unique mutations were identified, among which five were reported as stabilizing while 16 were destabilizing revealed through mCSM, DynaMut 2.0, and I-Mutant servers. Protein-protein docking with Angiotensin-converting enzyme 2 (ACE2) and monoclonal antibody (4A8) revealed that mutation G446V in the receptor-binding domain; R102S and G181V in the N-terminal domain (NTD) significantly affected the binding and thus increased the infectivity. The interaction pattern also revealed significant variations in the hydrogen bonding, salt bridges and non-bonded contact networks. The structural-dynamic features of these mutations revealed the global dynamic trend and the finding energy calculation further established that the G446V mutation increases the binding affinity towards ACE2 while R102S and G181V help in evading the host immune response. The other mutations reported supplement these processes indirectly. The binding free energy results revealed that wild type-RBD has a TBE of -60.55 kcal/mol while G446V-RBD reported a TBE of -73.49 kcal/mol. On the other hand, wild type-NTD reported -67.77 kcal/mol of TBE, R102S-NTD reported -51.25 kcal/mol of TBE while G181V-NTD reported a TBE of -63.68 kcal/mol. Conclusions: In conclusion, the current findings revealed basis for higher infectivity and immune evasion associated with the aforementioned mutations and structure-based drug discovery against such variants.

Diversity of Rotavirus Strains among Children with Acute Diarrhea in Karachi, Pakistan.

One of the common viral pathogens in infectious diarrhea is Rotavirus; in developing countries, it is a primary cause of deaths in children less than five years of age. This study was planned to find out the etiologic agents of acute watery diarrhea. In this study, 1465 stool samples were analyzed with the symptoms of acute diarrhea. Demographic data analysis showed no. of episodes of diarrhea, vomiting, and fever. All samples were checked by ELISA technique for the presence of Rotavirus circulating strains. More than 6% patients were found to be positive with Rotavirus. Common Rotavirus genotypes, including G2P4, G2P6, G3P4, G8P4, G8P6, G9P4, and G10P4, were detected in patients through RT-PCR. This study concluded that detection of rotavirus strain diversity and management of diarrheal patients may identify assortment of emerging strains and reduce emergence of antimicrobial resistance and repeated episodes of diarrhea, which may also help to avoid and manage the essential nutrients lost leading to malnutrition and stunted growth, as well as to reduce high mortality rate in young children less than five years.

Blocking key mutated hotspot residues in the RBD of the omicron variant (B.1.1.529) with medicinal compounds to disrupt the RBD-hACE2 complex using molecular screening and simulation approaches.

A new variant of SARS-CoV-2 known as the omicron variant (B.1.1.529) reported in South Africa with 30 mutations in the whole spike protein, among which 15 mutations are in the receptor-binding domain, is continuously spreading exponentially around the world. The omicron variant is reported to be highly contagious with antibody-escaping activity. The emergence of antibody-escaping variants is alarming, and thus the quick discovery of small molecule inhibitors is needed. Hence, the current study uses computational drug screening and molecular dynamics simulation approaches (replicated) to identify novel drugs that can inhibit the binding of the receptor-binding domain (RBD) with hACE2. Screening of the North African, East African and North-East African medicinal compound databases by employing a multi-step screening approach revealed four compounds, namely (-)-pipoxide (C1), 2-(p-hydroxybenzyl) benzofuran-6-ol (C2), 1-(4-hydroxy-3-methoxyphenyl)-2-{4-[(E)-3-hydroxy-1-propenyl]-2-methoxyphenoxy}-1,3-propanediol (C3), and Rhein (C4), with excellent anti-viral properties against the RBD of the omicron variant. Investigation of the dynamics demonstrates stable behavior, good residue flexibility profiles, and structural compactness. Validation of the top hits using computational bioactivity analysis, binding free energy calculations and dissociation constant (K D) analysis also indicated the anti-viral properties of these compounds. In conclusion, this study will help in the design and discovery of novel drug therapeutics, which may be used against the emerging omicron variant of SARS-CoV-2.