Pharmacologically induced production of fetal hemoglobin (HbF) is a pragmatic therapeutic strategy for the reduction of globin chain imbalance and improving the clinical severities of patients with β-hemoglobinopathies. To identify highly desirable new therapeutic HbF-inducing agents, we screened functionally diverse ten monoterpenes, as molecular entities for their potent induction and erythroid differentiation ability in human erythroleukemia cell line (K562) and transgenic mice. Benzidine hemoglobin staining demonstrated six compounds to have significantly induced erythroid differentiation of K562 cells in a dose and time-dependent manner. This induction paralleled well with the optimal accumulated quantity of total hemoglobin in treated cultures. The cytotoxic studies revealed that three (carvacrol, 3-carene, and 1,4-cineole) of the six compounds with their maximal erythroid expansion ability did not affect cell proliferation and were found non-toxic. Four compounds were found to have high potency, with 4-8-fold induction of HbF at both transcriptional and protein levels in vitro. Subsequently, an in vivo study with the three active non-cytotoxic compounds showed significant overexpression of the γ-globin gene and HbF production. Carvacrol emerged as a lead HbF regulator suggested by the increase in expression of γ-globin mRNA content (5.762 ± 0.54-fold in K562 cells and 5.59 ± 0.20-fold increase in transgenic mice), accompanied by an increase in fetal hemoglobin (F-cells) levels (83.47% in K562 cells and 79.6% in mice model). This study implicates monoterpenes as new HbF inducing candidates but warrants mechanistic elucidation to develop them into potential therapeutic drugs in β-thalassemia and sickle cell anemia.The infectious coronavirus disease (COVID-19) pandemic, caused by the coronavirus SARS-CoV-2, appeared in December 2019 in Wuhan, China, and has spread worldwide. As of today, more than 46 million people have been infected and over 1.2 million fatalities. With the purpose of contributing to the development of effective therapeutics, we performed an in silico determination of binding hot-spots and an assessment of their druggability within the complete SARS-CoV-2 proteome. All structural, non-structural, and accessory proteins have been studied, and whenever experimental structural data of SARS-CoV-2 proteins were not available, homology models were built based on solved SARS-CoV structures. Several potential allosteric or protein-protein interaction druggable sites on different viral targets were identified, knowledge that could be used to expand current drug discovery endeavors beyond the currently explored cysteine proteases and the polymerase complex. It is our hope that this study will support the efforts of the scientific community both in understanding the molecular determinants of this disease and in widening the repertoire of viral targets in the quest for repurposed or novel drugs against COVID-19.Oxysterols are cholesterol metabolites with multiple functions in controlling cellular homeostasis. In particular, 27-hydroxycholesterol (27-OH-Chol) has been shown to regulate a variety of physiological functions, but little is known about its uptake, intracellular trafficking, and efflux from cells. This is largely due to a lack of suitable analogs of 27-OH-Chol, which mimic this oxysterol closely. Here, we present the intrinsically fluorescent 27-hydroxy-cholestatrienol (27-OH-CTL), which differs from 27-OH-Chol only by having two additional double bonds in the steroid ring system. Based on molecular dynamics (MD) simulations, we show that 27-OH-CTL possesses almost identical membrane properties compared to 27-OH-Chol. By comparative imaging of 27-OH-CTL and of the cholesterol analogue cholestatrienol (CTL) in living cells, we assess the impact of a single hydroxy group on sterol trafficking. We find that human fibroblasts take up more CTL than 27-OH-CTL, but efflux the oxysterol analogue more efficiently. For both sterols, efflux includes shedding of vesicles from the plasma membrane. Intracellular, 27-OH-CTL accumulates primarily in lipid droplets (LDs), while CTL is mostly found in endosomes and lysosomes. Using fluorescence recovery after photobleaching (FRAP), we find for both sterols a rapidly exchanging pool, which moves orders of magnitude faster than sterol containing vesicles and LDs. In summary, by applying a new fluorescent derivative of 27-OH-Chol we demonstrate that human cells can distinguish sterols based on a single hydroxy group in the side chain, resulting in different transport itineraries, dynamics, and efflux kinetics. Both intrinsically fluorescent cholesterol and oxysterol analogues show rapid non-vesicular transport in human fibroblasts.Apolipoprotein D (ApoD) is a lipocalin superfamily member that plays important roles in the transport of small hydrophobic molecules, lipid metabolism, and stress resistance. Cuticular hydrocarbons are the principal components of the epicuticular lipid layer and play a critical role in water retention against environmental desiccation stress; however, the mechanism underlying the role of ApoD in insect desiccation tolerance has not yet been elucidated. Here, we report the molecular constitution, functional analysis, and phylogenetic relationship of the ApoD gene in Acyrthosiphon pisum (ApApoD). We found that ApApoD was transcribed throughout the life cycle of A. pisum, but was prominently expressed in the embryonic period and abdominal cuticle. In addition, we optimized the dose and silencing duration of RNAi, observing that RNAi against ApApoD significantly reduced the levels of both internal and cuticular hydrocarbons and adult fecundity. Moreover, cuticular hydrocarbon deficiency increased the sensitivity of aphids to desiccation stress and reduced their survival time, while desiccation stress significantly increased ApApoD expression. Lapatinib Together, it is confirmed that ApApoD participates in regulating cuticular hydrocarbon content of aphids under desiccation stress and is crucial for aphid reproduction. Therefore, the ApApoD gene of A. pisum may be a potential target for RNAi-based insect pest control due to its involvement in cuticular hydrocarbon accumulation and reproduction.