In silico fragment-based design and pharmacophore modelling of therapeutics against dengue virus envelope protein.

Unlabelled: Dengue virus, an arbovirus of genus Flavivirus, is an infectious disease causing organisms in the tropical environment leading to numerous deaths every year. No therapeutic is available against the virus till date with only symptomatic relief available. Here, we have tried to design therapeutic compounds from scratch by fragment based method followed by pharmacophore based modelling to find suitable similar structure molecules and validated the same by MD simulation, followed by binding energy calculations and ADMET analysis.

Repurposing of FDA-approved drugs against oligomerization domain of dengue virus NS1 protein: a computational approach.

Dengue fever is a serious health hazard on a global scale and its primary causative agent is the dengue virus (DENV). The non-structural protein 1 (NS1) of DENV plays a pivotal role in pathogenesis. It is associated with several autoimmune events, endothelial cell apoptosis, and vascular leakage, which increase mainly during the critical phase of infection.

Repurposing of therapeutic antibodies against dengue virus envelope protein receptor binding domain.

Dengue virus (DENV) is the leading cause of numerous deaths every year due to its high infectivity. In this study we have tried to target the DENV envelope protein receptor binding domain, the region crucial for binding to host receptors which leads to membrane fusion and entry of the viral genome into the human host cell. We have taken 13 known FDA approved antiviral therapeutic antibodies from therapeutic antibody database and tried to repurpose them against the DENV envelope protein.

A mechanistic study on the tolerance of PAM distal end mismatch by SpCas9.

The therapeutic application of CRISPR-Cas9 is limited due to its off-target activity. To have a better understanding of this off-target effect, we focused on its mismatch-prone PAM distal end. The off-target activity of SpCas9 depends directly on the nature of mismatches, which in turn results in deviation of the active site of SpCas9 due to structural instability in the RNA-DNA duplex strand.

Peptide based vaccine designing against endemic causing mammarenavirus using reverse vaccinology approach.

The rodent-borne Arenavirus in humans has led to the emergence of regional endemic situations and has deeply emerged into pandemic-causing viruses. Arenavirus have a bisegmented ambisense RNA that produces four proteins: glycoprotein, nucleocapsid, RdRp and Z protein. The peptide-based vaccine targets the glycoprotein of the virus encountered by the immune system.

Computational Insights into the Conformational Dynamics of HIV-1 Vpr in a Lipid Bilayer for Ion Channel Modeling.

HIV-1 Vpr is a multifunctional accessory protein consisting of 96 amino acids that play a critical role in viral pathogenesis. Among its diverse range of activities, Vpr can create a cation-selective ion channel within the plasma membrane. However, the oligomeric state of this channel has not yet been elucidated.

Repurposing of drugs targeting heparan sulphate binding site of dengue virus envelope protein: an in silico competitive binding study.

Dengue virus, an arbovirus, leads to millions of infections every year ultimately leading to a high rate of mortality. Highly effective and specific therapeutic option is not available till date to combat viral infection. One of the first stages in the virus lifecycle encompasses the viral entry into the host cell which is mediated by the interaction between heparan sulphate and the Dengue virus envelope protein in turn leading to the interaction between the envelope protein receptor binding domain and host cell receptors.

In silico designing of an epitope-based peptide vaccine cocktail against Nipah virus: an Indian population-based epidemiological study.

Nipah virus, a zoonotic virus from the family Paramyxoviridae has led to significant loss of lives till date with the most recent outbreak in India reported in Kerala. The virus has a considerably high mortality rate along with lack of characteristic symptoms which results in the delay of the virus detection. No specific vaccine is available for the virus although monoclonal antibody treatment has been seen to be effective along with favipiravir.

Ascorbic acid modulates immune responses through Jumonji-C domain containing histone demethylases and Ten eleven translocation (TET) methylcytosine dioxygenase.

Ascorbic acid is a redox regulator in many physiological processes. Besides its antioxidant activity, many intriguing functions of ascorbic acid in the expression of immunoregulatory genes have been suggested. Ascorbic acid acts as a co-factor for the Fe -containing α-ketoglutarate-dependent Jumonji-C domain-containing histone demethylases (JHDM) and Ten eleven translocation (TET) methylcytosine dioxygenasemediated epigenetic modulation.

Exploring the chemical space for potential inhibitors against cell surface binding protein of Mpox virus using molecular fingerprint based screening approach.

Mpox virus is the latest member of the Poxviridae family of which small pox virus is a member. Monekypox virus has led to thousands of infections across the globe. Poxvirus gains entry into the cell making use of glycosaminoglycans like chondroitin sulphate and heparan sulphate.

Computer-aided de novo design and optimization of novel potential inhibitors of HIV-1 Nef protein.

Nef is a small accessory protein pivotal in the HIV-1 viral replication cycle. It is a multifunctional protein and its interactions with kinases in host cells have been well characterized through many in vitro and structural studies. Nef forms a homodimer to activate the kinases and subsequently the phosphorylation pathways.

Repurposing of drug molecules from FDA database against Hepatitis C virus E2 protein using ensemble docking approach.

Hepatitis C virus, a member of the Flaviviridae family and genus Hepacivirus, is an enveloped, positively single stranded RNA virus. Its surface consists of a heterodimer of E1 and E2 proteins which play a crucial role in receptor binding and membrane fusion. In this study we have used in silico virtual screening by utilizing ensemble docking on the approved drugs.

investigation of binding propensity of hematoxylin derivative and damnacanthal for their potential inhibitory effect on HIV-1 Vpr from different subtypes.

HIV-1, the causative agent of AIDS leads to many deaths worldwide though few options are available as therapeutics. To deal with the continuous mutation in the virus genome, requirement of new drugs is always there. Subtype variation plays a crucial role in case of HIV-1 therapeutics development.

characterization, molecular docking, and dynamic simulation of a novel fungal cell-death suppressing effector, MoRlpA as potential cathepsin B-like cysteine protease inhibitor during rice blast infection.

The blast fungus is one of the most notorious pathogens affecting rice production worldwide. The cereal killer employs a special class of small secreted proteins called effectors to manipulate and perturb the host metabolism. In turn, the host plants trigger effector-triggered immunity (ETI) via localized cell death and hypersensitive response (HR).

In silico study on miRNA regulation and NSs protein interactome characterization of the SFTS virus.

Severe fever with thrombocytopenia syndrome causing virus i.e. SFTS virus has increased in the last few years.

Prediction of infectivity of SARS-CoV-2 virus based on Spike-hACE-2 interaction.

The COVID-19 pandemic caused by SARS-CoV-2 results almost 3 M death worldwide and till continuing in spite of having several vaccine against the virus. One of the main reasons is the mutations occur in the virus to cope with the environment. Detail study of genomics and proteomics level of each components may help to combat the situation.

Designing of nanobodies against Dengue virus Capsid: a computational affinity maturation approach.

Dengue virus, an arbovirus, is one of the most prevalent diseases in the tropical environment and leads to huge number of casualties every year. No therapeutics are available till date against the viral disease and the only medications provide symptomatic relief. In this study, we have focused on utilizing conventional nanobodies and repurposing them for Dengue.

An insight into the binding mechanism of Viprinin and its morpholine and piperidine derivatives with HIV-1 Vpr: molecular dynamics simulation, principal component analysis and binding free energy calculation study.

HIV-1 Vpr is an accessory protein responsible for a plethora of functions inside the host cell to promote viral pathogenesis. One of the major functions of Vpr is the G cell cycle arrest. Among several small molecule inhibitors, Viprinin, a coumarin derivative, has been shown to specifically inhibit the G cell cycle arrest activity of Vpr thus making it an excellent choice for a lead molecule to design antiretroviral drug.

In Silico Study of Mutational Stability of SARS-CoV-2 Proteins.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), an enveloped RNA virus transmits by droplet infection thus affects the respiratory system. Different genomes have been reported globally for SARS-CoV-2 with moderate level of mutation which makes it harder to combat the virus. Mutational profiling and the relevant evolutionary aspect of coronavirus proteins namely spike glycoprotein, membrane protein, envelope protein, nucleoprotein, ORF1ab, ORF3a, ORF6, ORF7a, ORF7b and ORF8 were studied by in silico experiments.

Exploring the intrinsic dynamics of SARS-CoV-2, SARS-CoV and MERS-CoV spike glycoprotein through normal mode analysis using anisotropic network model.

COVID-19 caused by SARS-CoV-2 have become a global pandemic with serious rate of fatalities. SARS-CoV and MERS-CoV have also caused serious outbreak previously but the intensity was much lower than the ongoing SARS-CoV-2. The main infectivity factor of all the three viruses is the spike glycoprotein.

In silico designing of peptide based vaccine for Hepatitis viruses using reverse vaccinology approach.

Five different Hepatitis virus from different viral species cause viral-hepatitis, which is a life threatening disease leading to a high number of loss of lives every year. The mode of infection and transmission is different for each species and mostly spreads by direct contact and body fluids (for HBV and HCV). No such vaccine is available that can cure all types of Hepatitis with cross-protection.