Abstract We study the CaM-peptide interactions for four CaM-related peptides with different calcium equivalents, using the hCaM-M124C-mBBr biosensor and Molecular Dynamics (MD). Due to the high sensitivity of the biosensor, we were able to calculate five K ds based on the number of calcium equivalents for each peptide, showing a directly proportional relationship between the degree of calcium saturation

Abstract Interleukin 1 Receptor type I (IL-1RI) is a multi-domain transmembrane receptor that triggers the inflammatory response. Understanding its detailed mechanism of action is crucial for treating immune disorders. IL-1RI is activated upon formation of its functional assembly that occurs by binding of the IL-1 cytokine and the accessory protein (Il-1RAcP) to it. X-ray crystallography, small-Angle

Abstract COVID-19 is a novel severe acute respiratory syndrome coronavirus. Currently, there is no effective treatment and vaccines seem to be the solution in the future. Virtual screening of potential drugs against the S protein of severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) has provided small molecular compounds with a high binding affinity. Unfortunately, most of these drugs do

Abstract Chemokines are the large family of chemotactic cytokines that play an important role in leukocyte movement and migration stimulation. Until now, several antibody-cytokine (chemokine) fusion proteins have been investigated in clinical trials because of their ability to evoke the circulating leukocytes far from the tumor site. In this case, creating the concentration gradient regarding the chemokine

Abstract The hepatitis C virus is a communicable disease that gradually harms the liver leading to cirrhosis and hepatocellular carcinoma. Important therapeutic interventions have been reached since the discovery of the disease. However, its resurgence urges the need for new approaches against this malady. The NS4B receptor is one of the important proteins for Hepatitis C Virus RNA replication that

Abstract Glucagon-like peptide-1 (GLP-1) is involved in glucose-stimulated insulin secretion and weight regulating actions through the activation of the GLP-1 receptor (GLP-1R). Clinical effectiveness of GLP-1 mimetics is effective in improving glucose control in patients. Thus, identifying and developing orally active small-molecule agonists are highly desirable. This study summarizes the structure-function

Abstract Coronavirus Disease 2019 (COVID-19) has infected more than thirty five million people worldwide and caused nearly 1 million deaths as of October 2020. The microorganism causing COVID-19 was named as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2 or 2019-nCoV). The aim of this study was to investigate the interactions of twenty-three phytochemicals belonging to different flavonoid

Abstract To confront a disease like Alzheimer’s disease having complex pathogenesis, development of multitarget-directed ligands has emerged as a promising drug discovery approach. In our endeavor towards the development of multitarget-directed ligands for Alzheimer’s disease, a series of indoloquinoxaline derivatives were designed and synthesized. In vitro cholinesterase inhibition studies revealed

Abstract 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

Abstract COVID-19, emerged at the end of 2019 have dramatically threatened the health, economy, and social mobility of people around the world and till date no medication is available for its treatment. An amazing herb, Nigella sativa, having antiviral, antihypertensive, anti- diarrhoeal, analgesics, and anti-bacterial properties, needs to be explored for its efficacy against SARS-CoV-2, the causative

Abstract The p53 gene is mutated in greater than 50% of several human cancers including bladder urothelial carcinoma, lung adenocarcinoma, colorectal carcinoma, and oral cancer. Mutations in the p53 gene occur predominantly in the DNA-binding domain causing loss of function and accumulation of dysfunctional p53 protein in tumors by hetero-oligomerization with the wild type p53. Thus an in silico approach

Abstract Brassica juncea is an important oil seed crop. The productivity of this plant, however, is known to be low due to the attack of plant pathogens. The plant chitinase-IV is known to hydrolyse the chitin present in the cell walls of the plant pathogens and thus enhance the plant defense systems. In this connection, studies were carried out by us on the prediction and characterization of the 3D

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been responsible for the current global pandemic that has caused a death toll of >1.12 million worldwide and number continues to climb in several countries. Currently, there are neither specific antiviral drugs nor vaccines for the treatment and prevention of COVID-19. We screened in silico, a group of natural spice and herbal

Abstract In the present study, 4-[(E)-(2-chorobenzylidene)amino]-3-(2-chlorobenzyl)-1H-1,2,4-triazole-5(4H)-thione (CAC) was characterized by spectroscopic investigations. The complete vibrational assignments of frequencies based on PED analysis was determined by DFT through ωB97X-D method with the level of 6-31g(d) basis and compared with experimental values. Recently nanocluster based drug delivery

Abstract Studies have shown that in cancer cells, there is an increased T-type calcium channel (TTCC) expression compared to healthy cells. Therefore, the studies targeting TTCC for cancer therapy have shown many positive outcomes. Here, we have used TTA-A2- a potent TTCC inhibitor as a test drug, and paclitaxel (PTX)- a tubule-binding anti-cancer agent as a positive control. Blocking TTCC has shown

Abstract Osteoarthritis (OA) is a degenerative disease which affects a large number of individuals. Collagenases, which belong to a class of metalloproteases (MMPs), are responsible for the degradation of cartilage manifested in OA. Inhibition of the catalytic domains of these MMPs is one of the important therapeutic strategies proposed for the prevention of OA. The main objective of this work is to

Abstract At present, there is no cure or vaccine for the devastating new highly infectious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that has affected people globally. Herein, we identified potent phytocompounds from two antiviral plants Momordica charantia L. and Azadirachta indica used locally for the treatment of viral and parasitic infections. Structure-based virtual screening

Abstract COVID-19, which is caused by a novel coronavirus known as SARS-CoV-2, has spread rapidly around the world, and it has infected more than 29 million individuals as recorded on 16 September 2020. Much effort has been made to stop the virus from spreading, and there are currently no approved pharmaceutical products to treat COVID-19. Here, we apply an in silico approach to investigate more than

Abstract Haptoglobin related protein (Hpr) is a component of the trypanosome lytic factor (TLF), a complex acting in the innate immune response against African trypanosomes. Like haptoglobin (Hp), Hpr binds hemoglobin (Hb) in the blood, but unlike Hp, Hpr does not bind the CD163 receptor. Moreover, unlike Hp, Hpr retains the N-terminal signal peptide that is required for the association with Apolipoprotein

Abstract The protein–protein interactions (PPIs) in the biological systems are important to maintain a number of cellular processes. Several disorders including cancer may be developed due to dysfunction in the assembly of PPI networks. Hence, targeting intracellular PPIs can be considered as a crucial drug target for cancer therapy. Among the enormous and diverse group of cancer-enabling PPIs, the

Abstract In December 2019, a new coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to the outbreak of a pulmonary disease called COVID-19, which killed thousands of people worldwide. Therefore, the necessity to find out the potential therapeutic pharmaceuticals is imperious. This study investigates the inhibitory effect of SARS-CoV-2 3-chymotrypsin-like protease (3CLpro)

Abstract Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an ongoing global health emergency. Repurposing of approved pharmaceutical drugs for COVID-19 treatment represents an attractive approach to quickly identify promising drug candidates. SARS-CoV-2 main protease (Mpro) is responsible for the maturation of viral functional proteins making

Abstract The outbreak of COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS CoV-2), represents a pandemic threat to global public health. To date, ∼530,000 people died of this disease worldwide. Presently, researchers/clinicians are adopting the drug repurposing strategy to combat this disease. It has also been observed that some repurposed anti-viral drugs may serve as potent

Abstract The high dependency and surplus use of agrochemical products have liberated enormous quantities of toxic halogenated pollutants into the environment and threaten the well-being of humankind. Herein, this study performed molecular docking, molecular dynamic (MD) simulations, molecular mechanics-Poisson Boltzmann Surface Area (MM-PBSA) calculations on the DehH2 from Bacillus thuringiensis, to

Abstract The nucleocapsid (N) protein from Peste des petits ruminants virus enwraps the nascent genomic RNA primarily to protect it from cellular enzymatic degradation. Here, we have combined molecular modeling and 1 μs long Gaussian accelerated molecular dynamics simulations to study the structural and conformational properties of the apo N-protein and three protein-RNA complexes, namely wild type

Abstract There are a significant number of cases whereby cancer patients belonging to the old age group additionally suffer from cognition decline (a hallmark feature of Alzheimer’s disease). Hence, it is understandable that it would be a boon if certain drug molecules could provide health benefits to a patient suffering from cancer as well as Alzheimer’s disease. The objective of the work was to identify

Abstract COVID-19 and its causative organism SARS-CoV2 that emerged from Wuhan city, China have paralyzed the world. With no clinically approved drugs, the global health system is struggling to find an effective treatment measure. At this crucial juncture, screening of plant-derived compounds may be an effective strategy to combat COVID-19. The present study investigated the binding affinity of phytocompounds

Abstract COVID-19 is a respiratory disease caused by SARS-CoV-2, an enveloped positive sense RNA virus. The SARS-CoV-2 spike glycoprotein, human angiotensin-converting enzyme 2 (ACE2) and human transmembrane protease serine 2 (TMPRSS2) are essential for the host cell-mediated viral entry. Targeting these proteins represent viable options to stop the first stage of infection and transmission. Hence

Abstract The single nucleotide polymorphisms (SNPs) are the common genetic variations in human genomes and act as markers for molecular susceptibility of complex traits and diseases in humans. Amino acid variations in the non-synonymous SNPs (nsSNPs) in coding and non-coding regions affect the function/structure of the proteins. The Peroxisome proliferator-activated receptor gamma (PPARγ or PPARG)

Abstract Human topoisomerase II alpha (TopoIIα) is a crucial enzyme involved in maintaining genomic integrity during the process of DNA replication and mitotic division. It is a vital therapeutic target for designing novel anticancer agents in targeted cancer therapy. Sulfones, members of organosulfur compounds, have been reported to possess various biological activities such as antimicrobial, anti-inflammatory

Abstract Given the highly contagious nature of SARS-CoV-2, it has resulted in an unprecedented number of COVID-19 infected and dead people worldwide. Since there is currently no vaccine available in the market, the identification of potential drugs is urgently needed to control the pandemic. In this study, 92 phytochemicals from medicinal plants growing in the Andean region were screened against SARS-CoV-2

Abstract Plant derived product can be used as other alternatives to currently used drugs for controlling chronic diseases like Diabetes mellitus. The potential of Coagulin L (a constituent of Withania coagulans) as dipeptidyl peptidase-4 (DPP-4) inhibitor was evaluated by molecular modelling study. It was observed that amino acid residues such as Glu205, Glu206, Tyr 547, His 740, and Try662 interacts

Abstract Inspired by the ‘There is no scientific evidence that turmeric prevents COVID-19’ statement made by WHO, the protective or therapeutic potential of the compounds in turmeric contents was investigated against COVID-19 with in silico methodology. The drugs used for experimental COVID-19 therapies were included in this study using the same method for comparison with turmeric components. The 30

Abstract The human Respiratory Syncytial Virus (hRSV) is one of the most common causes of acute respiratory diseases such as bronchiolitis and pneumonia in children worldwide. Among the viral proteins, the nucleoprotein (N) stands out for forming the nucleocapsid (NC) that functions as a template for replication and transcription by the viral polymerase complex. The NC/polymerase recognition is mediated

Abstract The β-Lactoglobulin (βLG) is a major whey protein that has the potential to bind various ligands; hence it is used as a model protein in protein-ligand interaction studies. Vitamin B12 is an essential nutrient for the human body, which helps in the synthesis of DNA, proteins, and the production of red blood cells. Binding interaction of vitamin B12 with βLG will help to understand the potency

  Communicated by Ramaswamy H. Sarma

Abstract Tuberculosis (TB) has been recently declared as a health emergency because of sporadic increase in Multidrug-resistant Tuberculosis (MDR-TB) problem throughout the world. TB causing bacteria, Mycobacterium tuberculosis has become resistant to the first line of treatment along with second line of treatment and drugs, which are accessible to us. Thus, there is an urgent need of identification

Abstract In the light reaction of oxygenic photosynthesis, plastocyanin (PC) and ferredoxins (Fd) are small/diffusible redox-active proteins playing key roles in electron transfer/transport phenomena. In the Z-scheme mechanistic purview, they are considered as specific affinity binding-based electron-relay agents, linking the functions of Cytochrome b 6 f (Cyt. b6f), Photosystem I (PS I) and Fd:NADPH

Abstract A novel coronavirus (SARS-CoV2) has caused a major outbreak in humans around the globe, and it became a severe threat to human healthcare than all other infectious diseases. Researchers were urged to discover and test various approaches to control and prevent such a deadly disease. Considering the emergency and necessity, we screened reported antiviral compounds present in the traditional

Abstract Despite the continued global spread of the current COVID-19 pandemic, the nonavailability of a vaccine or targeted drug against this disease is still prevailing. The most established mechanism of viral entry into the body is considered to be via angiotensin-converting enzyme 2 (ACE2) acting as a receptor for viral spike protein thereby facilitating its entry in the cell. However, ACE2 is also

Abstract Chikungunya virus (CHIKV) belongs to the alpha virus and it's infection in humans causes fever, known as chikungunya fever (CHIKF). It is a sudden onset of fever and may affect humans badly. The mode of transmission to human occurs due to the biting of the mosquitoes. Till date, thousands of humans are affected from this virus throughout the world. As on date, no promising medicine or vaccine

Abstract SARS-CoV-2 is the etiological agent of COVID-19 and responsible for more than 6 million cases globally, for which no vaccine or antiviral is available. Therefore, this study was planned to investigate the antiviral role of the active constituents against spike glycoprotein of SARS-CoV-2 as well as its host ACE2 receptor. Structure-based drug design approach has been used to elucidate the antiviral

Abstract HIV-1 protease (HIV-1 PR) is an essential enzyme for the replication process of its virus, and therefore considered an important target for the development of drugs against the acquired immunodeficiency syndrome (AIDS). Our previous study shows that the catalytic mechanism of subtype B/C-SA HIV-1 PR follows a one-step concerted acyclic hydrolysis reaction process using a two-layered ONIOM

Abstract Toxoplasma gondii is an opportunistic obligate parasite, ubiquitous around the globe with seropositivity rates that range from 10% to 90% and infection by the parasite of pregnant women causes pre-natal death of the foetus in most cases and severe neurodegenerative syndromes in some. No vaccine is currently available, and since drug-resistance is common among T. gondii strains, discovering

Abstract Oxidative stress plays an essential role in the regulation of vital processes in living organisms. Reactive oxygen species can react chemically with the constituents of the cells leading to irreversible damage. The first structure of the cell in contact with the environment that surrounds it is the membrane, which protects it and allows the exchange of substances. Some signals manifest when

Abstract In December 2019, the world observed an unexpected outbreak of an emerging disease named coronavirus (COVID-19) that was first reported in Wuhan city of Hubei province of China. Recent literature has shown the association between COVID-19 infection and derangement in the coagulation profile. In this paper, we are discussing thrombo-genesis, especially the role of the complement system in the

Abstract P-glycoprotein (ABCB1) and cytochrome P450 3A4 (CYP3A4) metabolize almost all known human immunodeficiency virus' protease inhibitor drugs (PIs). Over induction of these proteins’ activities has been linked to rapid metabolism of PIs which are then pumped out of the circulatory system, eventually leading to drug-resistance in HIV-positive patients. This study aims to determine, with the use

Abstract Alzheimer’s disease (AD) is a devastating neurodegenerative disease affecting 47 million people worldwide. While acetylcholinesterase (AChE) inhibitors such as donepezil and galantamine are leading drugs in the symptomatic treatment of AD, new AChE inhibitors continue to be explored for improved potency and selectivity. Herein, a molecular networking approach using high resolution (HR-MS)

Abstract Type II Diabetes Mellitus (DM) is caused by insulin resistance in peripheral tissue and impaired insulin secretion through a dysfunction of the pancreatic β-cell. Acarbose is an anti-DM drug, it is effective but its continuous use may lead to undesirable side effects. Hence, the development of novel drugs from natural source that have both anti-diabetic and anti-oxidant activities, with little

Abstract Cancer ranks in second place among the cause of death worldwide. Cancer progress in multiple stages of carcinogenesis and metastasis programs through complex pathways. Sex hormones and their receptors are the major factors in promoting cancer progression. Among them, G protein-coupled estrogen receptor-1 (GPER) has shown to mediate cellular signaling pathways and cancer cell proliferation

Abstract Amyloid-A mediated (AA) amyloidosis is the pathogenic byproduct of body’s prolonged exposure to inflammatory conditions. It is described by the aggregation of mutated/misfolded serum amyloid A1 (SAA1) protein in various tissues and organs. Genetic polymorphism G90D is suspected to cause AA amyloidosis, although the causal mechanism remains cryptic. Recent experimental findings insinuate that

Abstract This study investigates the molecular mechanisms underlying the anticancer activity of hesperidin and luteolin, isolated from Eriocephalus africanus, in the human breast carcinoma cell line (MCF-7). The viability of MCF-7 cells, upon treatment with hesperidin and luteolin, was evaluated using the 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide (MTT) cytotoxicity assay; apoptotic

Abstract Bombyx mori is an insect of economic importance in the production of silk. It often gets infected by Nosema bombycis, an intracellular parasite. The infection causes a fatal disease known as a Pebrine which affects the development of the worm. The infected larvae of silkworms are coated with brown spots and are unable to spin the silkworm thread. They lose appetite, become sluggish, opaque

Abstract Dysbiosis is a major cause of disease in an individual, generally initiated in the gastrointestinal tract. The gut, also known as the second brain, constitutes a major role in immune signaling. To study the immunity cascade, the Drosophila model was considered targeting the Imd pathway receptor (2F2L) located in the midgut. This receptor further initiates the immune signaling mechanism influenced

Abstract Recently, we designed and synthesized a subnanomolar, reversible, dual-binding site acetylcholinesterase (AChE) inhibitor which consists of the tacrine and aroylacrylic acid phenylamide moieties, mutually linked by eight methylene units. To further investigate the process of the molecular recognition between the AChE and its inhibitor, we performed six unconstrained molecular dynamics (MD)

Abstract In viral replication and transcription, the main protease (Mpro) of SARS-CoV-2 plays an important role and appears to be a vital target for drug design. In Mpro, there is a Cys–His catalytic dyad, and ligands that interact with the Cys145 assumed to be an effective approach to inhibit the Mpro. In this study, approximately 1400 cysteine-focused ligands were screened to identify the best candidates

Abstract Fusarium oxysporum causes significant economic losses in many crop plants by causing root rot, necrosis, and wilting symptoms. Homology and molecular dynamics studies are promising tools for the detection in F. oxysporum of the systemic resistance compound, salicylic acid, for control of the SKP1-CUL1-F-box protein complex. The structure of SKP1-CUL1-F-box subunit Skp1 from F. oxysporum is

Abstract Coronavirus disease 2019 (COVID-19), a highly contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has drastically changed the lifestyle of people around the globe. Due to the lack of specific and effective antiviral drugs, transmission of the disease increases exponentially and makes it more serious and harder to control. Drugs that were assumed to be

Abstract Biological membranes are essential to preserve structural integrity and regulate functional properties through the permeability of nutrients, pharmaceutical drugs, and neurotransmitters of a living cell. The movement of acetylated and amidated phenylalanine (NAFA) across 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) membrane bilayers

Abstract K-Ras is a small GTPase and acts as a molecular switch by recruiting GEFs and GAPs, and alternates between the inert GDP-bound and the dynamic GTP-bound forms. The amino acid at position 12 of K-Ras is a hot spot for oncogenic mutations (G12A, G12C, G12D, G12R, G12S, and G12V), disturbing the active fold of the protein, leading to cancer development. This study aimed to investigate the potential