The current outbreak of a novel coronavirus, named as SARS-CoV-2 causing COVID-19 occurred in 2019, is in dire need of finding potential therapeutic agents. Recently, ongoing viral epidemic due to coronavirus (SARS-CoV-2) primarily affected mainland China that now threatened to spread to populations in most countries of the world. In spite of this, there is currently no antiviral drug/ vaccine available against coronavirus infection, COVID-19. In the present study, computer-aided drug design-based screening to find out promising inhibitors against the coronavirus (SARS-CoV-2) leads to infection, COVID-19. The lead therapeutic molecule was investigated through docking and molecular dynamics simulations. In this, binding affinity of noscapines(23B)-protease of SARS-CoV-2 complex was evaluated through MD simulations at different temperatures. Our research group has established that noscapine is a chemotherapeutic agent for the treatment of drug resistant cancers; however, noscapine was also being used as anti-malarial, anti-stroke and cough-suppressant. This study suggests for the first time that noscapine exerts its antiviral effects by inhibiting viral protein synthesis. ARTICLE HISTORY

Coronavirus disease-2019 (COVID-19) is a global health emergency and the matter of serious concern, which has been declared a pandemic by WHO. Till date, no potential medicine/ drug is available to cure the infected persons from SARS-CoV-2. This deadly virus is named as novel 2019-nCoV coronavirus and caused coronavirus disease, that is, COVID-19. The first case of SARS-CoV-2 infection in human was confirmed in the Wuhan city of the China. COVID-19 is an infectious disease and spread from man to man as well as surface to man . In the present work, in silico approach was followed to find potential molecule to control this infection. Authors have screened more than one million molecules available in the ZINC database and taken the best two compounds based on binding energy score. These lead molecules were further studied through docking against the main protease of SARS-CoV-2. Then, molecular dynamics simulations of the main protease with and without screened compounds were performed at room temperature to determine the thermodynamic parameters to understand the inhibition. Further, molecular dynamics simulations at different temperatures were performed to understand the efficiency of the inhibition of the main protease in the presence of the screened compounds. Change in energy for the formation of the complexes between the main protease of novel coronavirus and ZINC20601870 as well ZINC00793735 at room temperature was determined on applying MM-GBSA calculations. Docking and molecular dynamics simulations showed their antiviral potential and may inhibit viral replication experimentally.

For the better management and control of the viral replication, it is essential to discover a potential molecule to combat Chikungunya virus (CHIKV). The work aims to find a potential antiviral molecule via its interactions with the non-structural protease (nsP3) of CHIKV. It plays a crucial role in intracellular replication. The best molecular interaction is based on the minimum total binding energy of hydrogen bonding, electrostatic interaction and van der Waals forces. It was found that Erythro-noscapines showed good binding affinity with nsP3 protease of CHIKV (PDB ID: 3GPO) and minimum total binding energy (-149.964 kcal/mol) to form a more stable complex i. e. 109-nsP3 protease of CHIKV. Erythro-noscapines (109, one of the derivatives of erythro-noscapine) showed better interaction than the reported molecules by different reseach groups via docking. The parameters for bioactivity score and Lipinski "Rule of Five" were calculated to estimate the pharmacokinetic properties of antiviral Erythro-noscapines and compared to others. 109 can be considered as a good candidate for antiviral replication against nsP3 protease of CHIKV. Molecular dynamics simulations on nsP3 protease of CHIKV with or without 109 was performed and studied. Further, binding free energies of potential noscapine-nsP3 protease of CHIKV based on Molecular Mechanics-Generalized Born Suface Area (MM-GBSA) was calculated. Further, toxicity of top 10 noscapines and reported molecules by different research groups was determined and then, density functional theory was applied to understand the singlet and triplet states of the 109.

Chikungunya fever is a major public health issue in India affecting millions of people and occurs due to Chikungunya. Chikungunya virus (CHIKV) is a single stranded RNA virus from the family of Togaviridae and genus alpha virus. It contain three structural proteins: glycosylated E1 and E2, embedded in the viral envelope, and a non-glycosylated nucleocapsid protein. Till date, researchers are working on inhibition of CHIKV but till now no cheap and effective medicine is available in the market. Therefore, the authors of this work thought of isoquinoline based noscapine to inhibit the nsP3 protease of CHIKV. The aim of the work is to understand the mechanism for the synthesis of noscapine theoretically using DFT. Further study the potential of all four isomers of noscapines {(13 (S,R), 14 (R,R), 15 (R,S) and 16 (S,S)} against nsP3 protease of CHIKV with the help of docking and MD simulation. The integrated e-pharmacophore binding affinity based virtual screening, docking and molecular dynamics simulation recognized four hits isomers as inhibition nsP3 protease of CHIKV. The docking energies of all the isomers of noscapine (13-16) with nsP3 protease CHIKV was found out to be more negative than baicalin (À8.06 kcal/mol) on selected sites. Amongst the isomers of noscapine, CMPD 13 possessed best binding affinity with four hydrogen bonding interactions. Further, ADME properties and blood-brain barrier permeability properties have been calculated. DFT studies of all the isomers of noscapine was investigated.

In adaptation biology of the discovery of the intracellular osmolytes, the osmolytes are found to play a central role in cellular homeostasis and stress response. A number of models using these molecules are now poised to address a wide range of problems in biology. Here, a combination of biophysical measurements and molecular dynamics (MD) simulation method is used to examine the effect of trimethylamine-N-oxide (TMAO) on stem bromelain (BM) structure, stability and function. From the analysis of our results, we found that TMAO destabilizes BM hydrophobic pockets and active site as a result of concerted polar and non-polar interactions which is strongly evidenced by MD simulation carried out for 250 ns. This destabilization is enthalpically favourable at higher concentrations of TMAO while entropically unfavourable. However, to the best of our knowledge, the results constitute first detailed unambiguous proof of destabilizing effect of most commonly addressed TMAO on the interactions governing stability of BM and present plausible mechanism of protein unfolding by TMAO.