Effects of Simulated Microgravity on Rat Reproductive System: Potential Benefits of Vitamin D3 Intervention.

Gravity in space can have a negative impact on the reproductive system. Given that the reproductive system is one of vitamin D's objectives, this study will use a simulated microgravity model to evaluate its impact on the rat reproductive system.Twenty-two male Wistar rats were allocated into four groups at random. Under microgravity circumstances, the rats were housed in both special and standard cages. Each group was then separated into two subgroups, one of which received vitamin D3 and the other did not. Blood was drawn twice to determine blood levels of vitamin D3, LH, FSH, and testosterone. Rat testes were isolated for histological analysis, as well as a piece of epididymis for sperm count and morphological examination.Microgravity had a detrimental effect on testicular tissue, resulting in lower serum levels of LH and testosterone (p-value < 0.001). Spermatogenesis was largely inhibited under microgravity. During microgravity conditions, however, vitamin D3 had a good effect on testicular structure, and the total number of sperm. Simulated microgravity affects the male reproductive system, compromising testicular morphology, sperm parameters, and hormonal balance. However, this study shows that vitamin D3 supplementation can act as a preventative strategy, minimizing the negative consequences of microgravity. The beneficial effect of vitamin D3 on testicular health and sperm quality implies that it may be useful in protecting male reproductive function in space-related situations.

A fragment-based drug discovery developed on ciclopirox for inhibition of Hepatitis B virus core protein: An in silico study.

The Hepatitis B virus (HBV) core protein is an attractive target for preventing capsid assembly and viral replication. Drug repurposing strategies have introduced several drugs targeting HBV core protein. This study used a fragment-based drug discovery (FBDD) approach to reconstruct a repurposed core protein inhibitor to some novel antiviral derivatives. Auto Core Fragment in silico Screening (ACFIS) server was used for deconstruction-reconstruction of Ciclopirox in complex with HBV core protein. The Ciclopirox derivatives were ranked based on their free energy of binding (ΔGB). A quantitative structure affinity relationship (QSAR) was established on the Ciclopirox derivatives. The model was validated by a Ciclopirox-property-matched decoy set. A principal component analysis (PCA) was also assessed to define the relationship of the predictive variable of the QSAR model. 24-derivatives with a ΔGB (-16.56±1.46 Kcal.mol-1) more than Ciclopirox was highlighted. A QSAR model with a predictive power of 88.99% (F-statistics = 9025.78, corrected df(25), Pr > F = 0.0001) was developed by four predictive descriptors (ATS1p, nCs, Hy, F08[C-C]). The model validation showed no predictive power for the decoy set (Q2 = 0). No significant correlation was observed between predictors. By directly attaching to the core protein carboxyl-terminal domain, Ciclopirox derivatives may be able to suppress HBV virus assembly and subsequent viral replication inhibition. Hydrophobic residue Phe23 is a critical amino acid in the ligand binding domain. These ligands share the same physicochemical properties that lead to the development of a robust QSAR mode. The same strategy may also be used for future drug discovery of viral inhibitors.

Druggability of cavity pockets within SARS-CoV-2 spike glycoprotein and pharmacophore-based drug discovery.

Aim: Virus spike glycoprotein of SARS-CoV-2 is a good target for drug discovery. Objective: To examine the potential for druggability of spike protein for pharmacophore-based drug discovery and to investigate the binding affinity of natural products with SARS-CoV-2 spike protein. Methods: Druggable cavities were searched though CavityPlus. A pharmacophore was built and used for hit identification. Autodock Vina was used to evaluate the hits' affinities. 10 chemical derivatives were also made from the chemical backbone to optimize the lead compound. Results: 10 druggable cavities were found within the glycoprotein spike. Only one cavity with the highest score at the binding site was selected for pharmacophore extraction. Hit identification resulted in the identification of 410 hits. Discussion: This study provides a druggable region within viral glycoprotein and a candidate compound to block viral entry.