The present-day world is severely suffering from the recently emerged SARS-CoV-2. The lack of prescribed drugs for the deadly virus has stressed the likely need to identify novel inhibitors to alleviate and stop the pandemic. In the present high throughput virtual screening study, we used in silico techniques like receptor-ligand docking, Molecular dynamic (MD), and ADME properties to screen natural compounds. It has been documented that many natural compounds display antiviral activities, including anti-SARS-CoV effect. The present study deals with compounds of Natural Product Activity and Species Source (NPASS) database with known biological activity that probably impedes the activity of six essential enzymes of the virus. Promising drug-like compounds were identified, demonstrating better docking score and binding energy for each druggable targets. After an extensive screening analysis, three novel multi-target natural compounds were predicted to subdue the activity of three/ more major drug targets simultaneously. Concerning the utility of natural compounds in the formulation of many therapies, we propose these compounds as excellent lead candidates for the development of therapeutic drugs against SARS-CoV-2.

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Background: Recruitment of peripheral proteins to the inner membrane complex (IMC) of the malaria parasite can be mediated by N-terminal acylation. Results: Characterization of substrate determinants and identification of an IMC-localized palmitoyl acyltransferase PfDHHC1. Conclusion: Residues close to palmitoylation sites interfere with specific IMC recruitment. PfDHHC1 represents an apicomplexan-specific PAT. Significance: Dissection of palmitoylation for protein recruitment to the inner membrane complex in P. falciparum.

Nipah virus (NiV) is an emerging zoonotic pathogen, reported for the recent severe outbreaks of encephalitis and respiratory illness in humans and animals, respectively. Many antiviral drugs have been discovered to inhibit this pathogen, but none of them were that much efficient. To overcome the complications associated with this severe pathogenic virus, we have designed a multi-epitope subunit vaccine using computational immunology strategies. Identification of structural and nonstructural proteins of Nipah virus assisted in the vaccine designing. The selected proteins are known to be involved in the survival of the virus. The antigenic binders (B-cell, HTL, and CTL) from the selected proteins were prognosticated. These antigenic binders will be able to generate the humoral as well as cell-mediated immunity. All the epitopes were united with the help of suitable linkers and with an adjuvant at the N-terminal of the vaccine, for the enhancement of immunogenicity. The physiological characterization, along with antigenicity and allergenicity of the designed vaccine candidates, was estimated. The 3D structure prediction and its validation were performed. The validated vaccine model was then docked and simulated with the TLR-3 receptor to check the stability of the docked complex. This next-generation approach will provide a new vision for the development of a high immunogenic vaccine against the NiV.

Hexameric DnaB type replicative helicases are essential for DNA strand unwinding along with the direction of replication fork movement. These helicases in general contain an amino terminal domain and a carboxy terminal domain separated by a linker region. Due to the lack of crystal structure of a full-length DnaB like helicase, the domain structure and function of these types of helicases are not clear. We have reported recently that Helicobacter pylori DnaB helicase is a replicative helicase in vitro and it can bypass Escherichia coli DnaC activity in vivo. Using biochemical, biophysical and genetic complementation assays, here we show that though the N-terminal region of HpDnaB is required for conformational changes between C6 and C3 rotational symmetry, it is not essential for in vitro helicase activity and in vivo function of the protein. Instead, an extreme carboxy terminal region and an adjacent unique 34 amino acid insertion region were found to be essential for HpDnaB activity suggesting that these regions are important for proper folding and oligomerization of this protein. These results confer great potential in understanding the domain structures of DnaB type helicases and their related function.