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 effective against COVID-19 have failed in various stages of clinical trials and this made the scientific community more disappointed. But, the race of researchers for developing new and effective antiviral to stop the disease progression still continues and our work is one among them. This study is an attempt to analyze the action of Tectoquinone and Acteoside; an important phytocompound, on SARS-CoV2 viral protease via in silico approach. The compounds were selected on the basis of their molecular docking values and they were subjected to molecular dynamics simulations about 50 ns to determine the stability and the thermodynamic feasibility between the target and the ligands. Binding energies like hydrogen bonding, hydrophobic and electrostatic interactions of the complexes were determined after MD simulations. The Pharmacokinetics and drug likeness evaluation of the compounds provide a strong evidence for the use of these compounds in developing drugs for clinical trials. Thus, the current study reveals the potential phytoconstituents present in Tectona grandis Linn to inhibit COVID-19 viral protease and thereby act as a lead therapeutic agent. Communicated by Ramaswamy H. Sarma

Novel fused pyran derivatives were synthesized and evaluated for anticancer activity against MCF7 (ATCC – HTB-22, breast), A549 (ATCC – CCL-185, lung), and HCT116 (ATCC – CCL-247, colorectal) cancer cell lines. Most compounds exhibited broad-spectrum activity. Among them, imidazole-containing derivatives 8a and 8b demonstrated potent anti-breast cancer activity with IC₅₀ values of 8.24 ± 0.19 μM and 4.22 ± 0.81 μM, respectively. Both compounds were nontoxic to MCR5 (ATCC – CCL-171, human diploid fibroblast) cell line. In vitro studies using MCF7 cells showed that 8a and 8b significantly reduced colony formation and inhibited spheroid progression. Cell cycle analysis revealed G1 arrest, a mechanism distinct from the standard drug etoposide. Furthermore, these compounds induced persistent DNA damage and both early and late apoptosis. In addition, ex ovo CAM assay revealed a significant reduction in new blood vessel formation over time compared to untreated controls. Network pharmacology identified EGFR, SRC, and GSK3B as potential targets, and molecular docking studies confirmed strong binding affinities to these proteins. This interaction is proposed to inhibit uncontrolled breast cancer cell growth. Additionally, the compounds exhibited favorable pharmacokinetic properties in silico. These findings suggest that novel fused pyran derivatives, particularly 8a and 8b, are promising candidates for further preclinical development as breast cancer therapeutics.

Hendra virus (HeV) is a highly pathogenic zoonotic paramyxovirus that poses a serious threat to human and equine health, yet no approved antivirals or vaccines currently exist. RNA-dependent RNA polymerase (RdRp) of Hendra virus represents a critical and attractive target for antiviral drug development, given its essential role in both viral genome replication and mRNA transcription. Due to the lack of a human homolog, it is more druggable and less likely to cause host toxicity. Its sequence conservation among related paramyxoviruses further highlights its potential for the development of broad-spectrum inhibitors. This study offers the first comprehensive computational analysis of the Hendra virus RdRp, potentially promising FDA-approved drugs as possible inhibitors. A homology model of RdRp was generated in the absence of experimental three-dimensional (3D) structure, followed by virtual screening and molecular dynamics (MD) simulations to evaluate the drug binding and stability. Based on the highest energy, four FDA-approved drugs selected were menadiol diphosphate (−49.88 kcal/mol), masoprocol (−39.69 kcal/mol), pamidronic acid (−34.29 kcal/mol), and dinoprostone (−46.90 kcal/mol). Furthermore, these compounds exhibited significant interactions with the catalytic GDNE motif. With strong conformational stability and pharmacokinetic profile, masoprocol and menadiol diphosphate showed the most stable and energetically favorable interactions within the RdRp active site. These findings suggest their potential as repurposed therapeutic candidates against Hendra virus infection and they provide a structural basis for the development of broad-spectrum paramyxovirus inhibitors, justifying additional experimental confirmation.