The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its new variants reported in different countries have posed a serious threat to human health and social fabrics worldwide. In addition, these new variants hindered the efforts of vaccines and other therapeutic developments. In this review article, we explained the emergence of new variants of SARS-CoV-2, their transmission risk, mortality rate, and, more importantly, the impact of each new variant on the efficacy of the developed vaccines reported in different literature and findings. The literature reported that with the emergence of new variants, the efficacy of different vaccines is declined, hospitalization and the risk of reinfection is increased. The reports concluded that the emergence of a variant that entirely evades the immune response triggered by the vaccine is improbable. The emergence of new variants and reports of re-infections are creating a more distressing situation and therefore demands further investigation to formulate an effective therapeutic strategy.

The human KRAS (Kirsten rat sarcoma) is an oncogene, involved in the regulation of cell growth and division. The mutations in the KRAS gene have the potential to cause normal cells to become cancerous in human lungs. In the present study, we focus on non-synonymous single nucleotide polymorphisms (nsSNPs), which are point mutations in the DNA sequence leading to the amino acid variants in the encoded protein. To begin with, we developed a pipeline to utilize a set of computational tools in order to obtain the most deleterious nsSNPs (Q22K, Q61P, and Q61R) associated with lung cancer in the human KRAS gene. Furthermore, molecular dynamics simulation and structural analyses of the 3D structures of native and mutant proteins confirmed the impact of these nsSNPs on the stability of the protein. Finally, the experimental results demonstrated that the structural stability of the mutant proteins was worse than that of the native protein. This study provides significant guidance for narrowing down the number of KRAS mutations to be screened as potential diagnostic biomarkers and to better understand the structural and functional mechanisms of the KRAS protein.

A.D. is a common disease among other neurodegenerative disorders primarily developing due to amyloid-β (Aβ) neurotoxicity derived from the amyloid-β protein precursor (AβPP). The amyloid precursor-like proteins 1 and 2 (APP1 and APLP2) biochemically behave similarly in many aspects to AβPP. We, therefore, proposed to test WGX-50 and Alpha-M for their interaction mechanism with APLP1 and APLP2 because both these drug candidate compounds previously showed inhibition of Aβ aggregation. We employed a comparative atomic investigation on Alpha-M and WGX-50 in complex with novel targets, i.e., APLP1 and APLP2, using biophysical and molecular simulation methods. The docking score was −6.83 kcal mol⁻¹ for Alpha-M–APLP1, −8.41 kcal mol⁻¹ for WGX-50–APLP1, −7.02 kcal mol⁻¹ for Alpha-M–APLP2 and −8.25 kcal mol⁻¹ for the WGX-50–APLP2 complex. Our results also elaborate that in the case of their interaction with both APLP1 and APLP2, the WGX-50 complex exhibits better stability than the APLP1/2-Alpha-M complexes during simulation. Furthermore, WGX50 in both APLP1 and APLP2 stabilized the internal flexibility upon binding in contrast to the Alpha-M complexes. The data showed that the BFE for Alpha-M–APLP1 was calculated to be −27.38 ± 0.93 kcal mol⁻¹, for WGX-50–APLP1 −39.65 ± 0.95 kcal mol⁻¹, for Alpha-M–APLP2 −24.80 ± 0.63 kcal mol⁻¹ while for WGX-50–APLP2 the BFE was −57.16 ± 1.03 kcal mol⁻¹ respectively. These results highlight that APLP2-WGX50 has greater binding energies in all four systems. PCA and FEL analysis further revealed variations in the dynamic behavior of these complexes. Overall, our findings demonstrate that WGX50 potentially acts as a more potent inhibitor for APLP1 and APLP2 than Alpha-M and thus shows the diverse pharmacological potential of WGX50. Due to its stable binding interaction, WGX50 might be a suitable candidate drug compound for targeting these precursors under pathological conditions.

The flavor complexity of red wine stems from diverse aroma compounds and their interactions. Key odorants 2,3,5-trimethylpyrazine (TMP) and furfuryl alcohol (FA) contribute roasted/earthy and sweet/caramel-like notes, respectively, collectively shaping the wine’s sensory profile. However, the mechanism underlying their olfactory interaction remains unclear. In this study, human sensory evaluation revealed a mutual synergistic enhancement between TMP and FA. Cellular models expressing cognate receptors OR5K1 (TMP-specific) and OR2W1 (FA-responsive) were established, with intracellular cAMP detection confirming receptor-level synergy. Further molecular simulations predicted non-competitive binding mechanisms, as both odorants occupied distinct sites within their respective receptor pockets, consistent with observed non-antagonistic synergy. This work elucidates the molecular perceptual mechanism underlying key wine aroma interactions, providing a novel theoretical framework for understanding red wine flavor complexity.