Exploring Niclosamide as a Multi-target Drug Against SARS-CoV-2: Molecular Dynamics Simulation Studies on Host and Viral Proteins.

Niclosamide has emerged as a promising repurposed drug against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In vitro studies suggested that niclosamide inhibits the host transmembrane protein 16F (hTMEM16F), crucial for lipid scramblase activity, which consequently reduces syncytia formation that aids viral spread. Based on other in vitro reports, niclosamide may also target viral proteases such as papain-like protease (PLpro) and main protease (Mpro), essential for viral replication and maturation.

Cost estimation of COVID Kavach test developed in 2020: A National Reference Laboratory initiative during early phase of Indian pandemic mitigation.

Background Objectives: A new indigenously developed technology, coronavirus disease (COVID) Kavach, an IgG immunoglobulin-based enzyme-linked immunosorbent assay (ELISA) kit, was developed in 2020 by the Indian Council of Medical Research-National Institute of Virology (ICMR-NIV), Pune, India. The primary objective of this study was to determine the total cost of development of COVID Kavach IgG ELISA and estimate the unit cost (UC) as well.

Methods: The total development cost (TDC) of COVID Kavach and its UC during the early phase of pandemic mitigation were estimated through a micro-costing approach from provider's perspective.

Cost-analysis of real time RT-PCR test performed for COVID-19 diagnosis at India's national reference laboratory during the early stages of pandemic mitigation.

Real-time reverse transcription polymerase chain reaction (rRT-PCR) is one of the most accurate and extensively used laboratory procedures for diagnosing COVID-19. This molecular test has high diagnostic accuracy (sensitivity and specificity) and is considered as the gold standard for COVID-19 diagnosis. During COVID-19 surge in India, rRT-PCR service was encouraged and supported by the government of India through existing healthcare setup at various levels of healthcare facilities.

3D QSAR pharmacophore-based virtual screening for the identification of potential inhibitors of tyrosinase.

Tyrosinase plays an important role in melanin biosynthesis and protects skin against ultraviolet radiations. Functional deficiency of tyrosinase results in serious dermatological diseases. Tyrosinase also participates in neuromelanin formation in the human brain, which leads to neurodegeneration resulting in Parkinson's disease.

Conformational preferences and structural analysis of hypermodified nucleoside, peroxywybutosine (o2yW) found at 37 position in anticodon loop of tRNA and its role in modulating UUC codon-anticodon interactions.

Hypermodified bases present at 3'-adjacent (37) position in anticodon loop of tRNA are well known for their contribution in modulating codon-anticodon interactions. Peroxywybutosine (o2yW), a wyosine family member, is one of such tricyclic modified bases observed at the 37 position in tRNA. Conformational preferences and three-dimensional structural analysis of peroxywybutosine have not been investigated in detail at atomic level.

A Bacteriophage Capsid Protein Is an Inhibitor of a Conserved Transcription Terminator of Various Bacterial Pathogens.

Rho is a hexameric molecular motor that functions as a conserved transcription terminator in the majority of bacterial species and is a potential drug target. Psu is a bacteriophage P4 capsid protein that inhibits Rho by obstructing its ATPase and translocase activities. In this study, we explored the anti-Rho activity of Psu for Rho proteins from different pathogens.

Idiosyncratic recognition of UUG/UUA codons by modified nucleoside 5-taurinomethyluridine, τm5U present at 'wobble' position in anticodon loop of tRNALeu: A molecular modeling approach.

Lack of naturally occurring modified nucleoside 5-taurinomethyluridine (τm5U) at the 'wobble' 34th position in tRNALeu causes mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS). The τm5U34 specifically recognizes UUG and UUA codons. Structural consequences of τm5U34 to read cognate codons have not been studied so far in detail at the atomic level.

Comparative Structural Dynamics of tRNA(Phe) with Respect to Hinge Region Methylated Guanosine: A Computational Approach.

Transfer RNAs (tRNAs) contain various uniquely modified nucleosides thought to be useful for maintaining the structural stability of tRNAs. However, their significance for upholding the tRNA structure has not been investigated in detail at the atomic level. In this study, molecular dynamic simulations have been performed to assess the effects of methylated nucleic acid bases, N (2)-methylguanosine (m(2)G) and N (2)-N (2)-dimethylguanosine (m 2 (2) G) at position 26, i.

The influence of hypermodified nucleosides lysidine and t(6)A to recognize the AUA codon instead of AUG: a molecular dynamics simulation study.

Hypermodified nucleosides lysidine (L) and N(6)-threonylcarbamoyladenosine (t(6)A) influence codon-anticodon interactions during the protein biosynthesis process. Lysidine prevents the misrecognition of the AUG codon as isoleucine and that of AUA as methionine. The structural significance of these modified bases has not been studied in detail at the atomic level.

Conformational Preferences of Modified Nucleoside 5-Taurinomethyluridine, τm(5)U Occur at 'wobble' 34th Position in the Anticodon Loop of tRNA.

Conformational preferences of hypermodified nucleoside 5-taurinomethyluridine 5'-monophoshate 'p-τm(5)U' (-CH2-NH2(+)-CH2-CH2-SO3(-)) have been investigated using semi-empirical RM1 method. Automated geometry optimization using ab initio molecular orbital HF-SCF (6-31G**) and DFT (B3LYP/6-31G**) calculations have also been made to compare the salient features. The RM1 preferred most stable conformation of 'p-τm(5)U' has been stabilized by hydrogen bonding interactions between O(11a)…HN(8), O1P(34)…HN(8), and O1P(34)…HC(10).

MD simulation studies to investigate iso-energetic conformational behaviour of modified nucleosides m(2)G and m(2) 2G present in tRNA.

Modified nucleic acid bases are most commonly found in tRNA. These may contain modifications from simple methylation to addition of bulky groups. Methylation of the four canonical nucleotide bases at a wide variety of positions is particularly prominent among the known modification.