Computational Assessment of Clinical Drugs against SARS-CoV-2: Foreseeing Molecular Mechanisms and Potent Mpro Inhibitors.

The emergence of new SARS-CoV-2 variants of concern (VOC) is a propulsion for accelerated potential therapeutic discovery. SARS-CoV-2's main protease (Mpro), essential for host cell viral replication, is a pre-eminent druggable protein target. Here, we perform extensive drug re-profiling of the comprehensive Excelra database, which compiles various under-trial drug candidates for COVID-19 treatment.

Immune targeting of filarial glutaredoxin through a multi-epitope peptide-based vaccine: A reverse vaccinology approach.

Despite the efforts of global programme to eliminate lymphatic filariasis (GPELF), the threat of lymphatic filariasis (LF) still looms over humanity in terms of long-term disabilities, and morbidities across the globe. In light of this situation, investigators have chosen to focus on the development of immunotherapeutics targeting the physiologically important filarial-specific proteins. Glutaredoxin (16.

Critical assessment of interactions between ct-DNA and choline-based magnetic ionic liquids: evidences of compaction.

Ionic liquids (ILs) have become an alternative green solvent for storage and for stability of DNA. However, an in-depth understanding of binding and molecular interactions between ILs and DNA is needed. In this respect, magnetic ILs (MILs) are promising due to their tunable physicochemical properties.

Can Duvelisib and Eganelisib work for both cancer and COVID-19? Molecular-level insights from MD simulations and enhanced samplings.

SARS-CoV-2 has caused severe illness and anxiety worldwide, evolving into more dreadful variants capable of evading the host's immunity. Cytokine storms, led by PI3Kγ, are common in cancer and SARS-CoV-2. Naturally, there is a yearning to see whether any drugs could alleviate cytokine storms for both.

evaluation of -adenosyl-L-homocysteine analogs as inhibitors of nsp14-viral cap N7 methyltranferase and PLpro of SARS-CoV-2: synthesis, molecular docking, physicochemical data, ADMET and molecular dynamics simulations studies.

A series of -adenosyl-L-homosysteine (SAH) analogs, with modification in the base and sugar moiety, have been designed, synthesized and screened as nsp14 and PLpro inhibitors of severe acute respiratory syndrome corona virus (SARS-CoV-2). The outcomes of ADMET (Adsorption, Distribution, Metabolism, Excretion, and Toxicity) studies demonstrated that the physicochemical properties of all analogs were permissible for development of these SAH analogs as antiviral agents. All molecules were screened against different SARS-CoV-2 targets using molecular docking.

Unmasking an Allosteric Binding Site of the Papain-like Protease in SARS-CoV-2: Molecular Dynamics Simulations of Corticosteroids.

To date, mechanistic insights into many clinical drugs against COVID-19 remain unexplored. Dexamethasone, a corticosteroid, is one of them. While treating the entire corticosteroid database, including vitamins D2 and D3, with cutting-edge computational techniques, several intriguing results are unfolded.

Post-Synthetic Modification of Zr-based Metal-Organic Frameworks with Imidazole: Variable Optical Behavior and Sensing.

UiO-66-NH -IM, a fluorescent metal-organic framework (MOF), was synthesized by post-synthetic modification of UiO-66-NH with 2-imidazole carboxaldehyde via a Schiff base reaction. It was examined using various characterization techniques (PXRD, FTIR, NMR, SEM, TGA, UV-Vis DRS, and photoluminescence spectroscopy). The emissive feature of UiO-66-NH -IM was utilized to detect volatile organic compounds (VOCs), metal ions, and anions, such as acetone, Fe , and carbonate (CO ).

Exploring antiviral potency of N-1 substituted pyrimidines against HIV-1 and other DNA/RNA viruses: Design, synthesis, characterization, ADMET analysis, docking, molecular dynamics and biological activity.

A novel series of pyrimidine derivatives, bearing modified benzimidazoles at N-1 position, has been designed, synthesized and screened as NNRTIs against HIV and as broad-spectrum antiviral agents. The molecules were screened against different HIV targets using molecular docking experiment. The docking results indicated that the molecules interacted well with the residues Lys101, Tyr181, Tyr188, Trp229, Phe227 and Tyr318 present in NNIBP of HIV-RT protein, formed quite stable complexes and, thus, behaved as probable NNRTIs.

Design, synthesis, antimicrobial activity, DFT, and molecular docking studies of pyridine-pyrazole-based dihydro-1,3,4-oxadiazoles against various bacterial and fungal targets.

Antimicrobial resistance which is increasing at an alarming rate is a severe public health issue worldwide. Hence, the development of novel antibiotics is an urgent need as microbes have developed resistance against available antibiotics. In search of novel antimicrobial agents, a convenient route for the preparation of substituted 3-(1-phenyl-3-(p-tolyl)-1H-pyrazol-4-yl)-1-(2-phenyl-5-(pyridin-3-yl)-1,3,4-oxadiazol-3(2H)-yl)prop-2-en-1-ones (6a-6o) has been adopted by using pyridine-3-carbohydrazide and various aromatic aldehydes.

Cell Surface Fibroblast Activation Protein-2 (Fap2) of as a Vaccine Candidate for Therapeutic Intervention of Human Colorectal Cancer: An Immunoinformatics Approach.

Colorectal cancer (CRC) is one of the most common cancers and is the second-highest in cancer-related deaths worldwide. The changes in gut homeostasis and microbial dysbiosis lead to the initiation of the tumorigenesis process. Several pathogenic gram-negative bacteria including are the principal contributors to the induction and pathogenesis of CRC.

Identification and Investigation of a Cryptic Binding Pocket of the P37 Envelope Protein of Monkeypox Virus by Molecular Dynamics Simulations.

The spread of the monkeypox virus has surged during the unchecked COVID-19 epidemic. The most crucial target is the viral envelope protein, p37. However, lacking p37's crystal structure is a significant hurdle to rapid therapeutic discovery and mechanism elucidation.

Insights into the binding mechanism of ascorbic acid and violaxanthin with violaxanthin de-epoxidase (VDE) and chlorophycean violaxanthin de-epoxidase (CVDE) enzymes.

Photosynthetic organisms have evolved to work under low and high lights in photoprotection, acting as a scavenger of reactive oxygen species. The light-dependent xanthophyll cycle involved in this process is performed by a key enzyme (present in the thylakoid lumen), Violaxanthin De-Epoxidase (VDE), in the presence of violaxanthin (Vio) and ascorbic acid substrates. Phylogenetically, VDE is found to be connected with an ancestral enzyme Chlorophycean Violaxanthin De-Epoxidase (CVDE), present in the green algae on the stromal side of the thylakoid membrane.

Reverse vaccinology assisted design of a novel multi-epitope vaccine to target Wuchereria bancrofti cystatin: An immunoinformatics approach.

Proteases are the critical mediators of immunomodulation exerted by the filarial parasites to bypass and divert host immunity. Cystatin is a small (∼15 kDa) immunomodulatory filarial protein and known to contribute in the immunomodulation strategy by inducing anti-inflammatory response through alternative activation of macrophages. Recently, Wuchereria bancrofti cystatin has been discovered as a ligand of human toll-like receptor 4 which is key behind the cystatin-induced anti-inflammatory response in major human antigen-presenting cells.

Potential targets of severe acute respiratory syndrome coronavirus 2 of clinical drug fluvoxamine: Docking and molecular dynamics studies to elucidate viral action.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has continued evolving for survival and adaptation by mutating itself into different variants of concern, including omicron. Several studies and clinical trials found fluvoxamine, an Food and Drug Administration-approved antidepressant drug, to be effective at preventing mild coronavirus disease 2019 (COVID-19) from progressing to severe diseases. However, the mechanism of fluvoxamine's direct antiviral action against COVID-19 is still unknown.

-graphyne as a promising anode material for Na-ion batteries: a first-principles study.

Lithium-ion batteries (LIBs) have emerged as a technological game-changer. Due to the rising price of lithium and the environmental concerns LIBs pose, their use is no longer viable. Sodium (Na) may be the best contender among the alternatives for replacing lithium.

Hydroxyalkynyl uracil derivatives as NNRTIs against HIV-1: predictions, synthesis, docking and molecular dynamics simulation studies.

To improve rationally the efficacy of the non-nucleoside human immunodeficiency virus (HIV-1) inhibitors, it is important to have a precise and detailed understanding of the HIV-1 reverse transcriptase (RT) and inhibitor interactions. For the 1-[(2-hydroxyethoxy) methyl]-6-(phenylthio) thymine (HEPT) type of nucleoside reverse transcriptase inhibitors (NNRTIs), the H-bond between the N-3H of the inhibitor and the backbone carbonyl group of K101 represents the major hydrophilic interaction. This H-bond contributes to the NNRTI binding affinity.

Designing efficient multi-epitope peptide-based vaccine by targeting the antioxidant thioredoxin of bancroftian filarial parasite.

Thioredoxin is a low molecular weight redox-active protein of filarial parasite that plays a crucial role in downregulating the host immune response to prolong the survival of the parasite within the host body. It has the ability to cope up with the oxidative challenges posed by the host. Hence, the antioxidant protein of the filarial parasite has been suggested to be a useful target for immunotherapeutic intervention of human filariasis.

Designing AbhiSCoVac - A single potential vaccine for all 'corona culprits': Immunoinformatics and immune simulation approaches.

The coronaviridae family has generated highly virulent viruses, including the ones responsible for three major pandemics in last two decades with SARS in 2002, MERS outbreak in 2012 and the current nCOVID19 crisis that has turned the world breadthless. Future outbreaks are also a plausible threat to mankind. As computational biologists, we are committed to address the need for a universal vaccine that can deter all these pathogenic viruses in a single shot.

Repurposing of FDA-approved drugs as potential inhibitors of the SARS-CoV-2 main protease: Molecular insights into improved therapeutic discovery.

With numerous infections and fatalities, COVID-19 has wreaked havoc around the globe. The main protease (Mpro), which cleaves the polyprotein to form non-structural proteins, thereby helping in the replication of SARS-CoV-2, appears as an attractive target for antiviral therapeutics. As FDA-approved drugs have shown effectiveness in targeting Mpro in previous SARS-CoV(s), molecular docking and virtual screening of existing antiviral, antimalarial, and protease inhibitor drugs were carried out against SARS-CoV-2 Mpro.

evidences on filarial cystatin as a putative ligand of human TLR4.

Cystatin is a small molecular weight immunomodulatory protein of filarial parasite that plays a pivotal role in downregulating the host immune response to prolong the survival of the parasite inside the host body. Hitherto, this protein is familiar as an inhibitor of human proteases. However, growing evidences on the role of cystatin in regulating inflammatory homeostasis prompted us to investigate the molecular reasons behind the explicit anti-inflammatory trait of this protein.

ACE-2-Derived Biomimetic Peptides for the Inhibition of Spike Protein of SARS-CoV-2.

SARS-CoV-2, a novel coronavirus causing overwhelming death and infection worldwide, has emerged as a pandemic. Compared to its predecessor SARS-CoV, SARS-CoV-2 is more infective for being highly contagious and exhibiting tighter binding with host angiotensin-converting enzyme 2 (hACE-2). The entry of the virus into host cells is mediated by the interaction of its spike protein with hACE-2.

Designing of a novel multi-epitope peptide based vaccine against Brugia malayi: An in silico approach.

In spite of the tremendous efforts of the World Health Organization, scientific and medical community to eradicate lymphatic filariasis (LF) within 2020, the disease is still taking a huge toll on mankind throughout the globe. The current therapeutic strategies and solution measures against this alarming condition are suffering from a number of limitations such as inadequate effectiveness of the drugs against the adult-stage parasites, low bioavailability, and emergence of resistance. Considering this situation, development of the new therapeutics are urgently needed to combat human LF, especially targeting the adult filarial nematodes.

Binding mechanism and structural insights into the identified protein target of COVID-19 and importin-α with effective drug ivermectin.

While an FDA approved drug Ivermectin was reported to dramatically reduce the cell line of SARS-CoV-2 by ∼5000 folds within 48 h, the precise mechanism of action and the COVID-19 molecular target involved in interaction with this in-vitro effective drug are unknown yet. Among 12 different COVID-19 targets along with Importin-α studied here, the RNA dependent RNA polymerase (RdRp) with RNA and Helicase NCB site show the strongest affinity to Ivermectin amounting -10.4 kcal/mol and -9.

Ivermectin, Famotidine, and Doxycycline: A Suggested Combinatorial Therapeutic for the Treatment of COVID-19.

At times, combination therapy has proven to be very effective. While no cure is available to date, herein we put forward with rationale and supporting evidence that if administrated simultaneously, a combination of FDA-approved drugs comprising ivermectin, famotidine, and doxycycline may provide robust chemoprophylaxis effective against COVID-19.

Alkylated benzimidazoles: Design, synthesis, docking, DFT analysis, ADMET property, molecular dynamics and activity against HIV and YFV.

A series of alkylated benzimidazole derivatives was synthesized and screened for their anti-HIV, anti-YFV, and broad-spectrum antiviral properties. The physicochemical parameters and drug-like properties of the compounds were assessed first, and then docking studies and MD simulations on HIV-RT allosteric sites were conducted to find the possible mode of their action. DFT analysis was also performed to confirm the nature of the hydrogen bonding interaction of active compounds.