A Clinical Update on SARS-CoV-2: Pathology and Development of Potential Inhibitors.

SARS-CoV-2 (severe acute respiratory syndrome) is highly infectious and causes severe acute respiratory distress syndrome (SARD), immune suppression, and multi-organ failure. For SARS-CoV-2, only supportive treatment options are available, such as oxygen supportive therapy, ventilator support, antibiotics for secondary infections, mineral and fluid treatment, and a significant subset of repurposed effective drugs. Viral targeted inhibitors are the most suitable molecules, such as ACE2 (angiotensin-converting enzyme-2) and RBD (receptor-binding domain) protein-based inhibitors, inhibitors of host proteases, inhibitors of viral proteases 3CLpro (3C-like proteinase) and PLpro (papain-like protease), inhibitors of replicative enzymes, inhibitors of viral attachment of SARS-CoV-2 to the ACE2 receptor and TMPRSS2 (transmembrane serine proteinase 2), inhibitors of HR1 (Heptad Repeat 1)-HR2 (Heptad Repeat 2) interaction at the S2 protein of the coronavirus, etc. Targeting the cathepsin L proteinase, peptide analogues, monoclonal antibodies, and protein chimaeras as RBD inhibitors interferes with the spike protein's ability to fuse to the membrane. Targeting the cathepsin L proteinase, peptide analogues, monoclonal antibodies, and protein chimaeras as RBD inhibitors interferes with the spike protein's ability to fuse to the membrane. Even with the tremendous progress made, creating effective drugs remains difficult. To develop COVID-19 treatment alternatives, clinical studies are examining a variety of therapy categories, including antibodies, antivirals, cell-based therapy, repurposed diagnostic medicines, and more. In this article, we discuss recent clinical updates on SARS-CoV-2 infection, clinical characteristics, diagnosis, immunopathology, the new emergence of variant, SARS-CoV-2, various approaches to drug development and treatment options. The development of therapies has been complicated by the global occurrence of many SARS-CoV-2 mutations. Discussion of this manuscript will provide new insight into drug pathophysiology and drug development.

Plasma Promotes Fungal Cellulase Production by Regulating the Levels of Intracellular NO and Ca2.

For the industrial-scale production of useful enzymes by microorganisms, technological development is required for overcoming a technical bottleneck represented by poor efficiency in the induction of enzyme gene expression and secretion. In this study, we evaluated the potential of a non-thermal atmospheric pressure plasma jet to improve the production efficiency of cellulolytic enzymes in Neurospora crassa, a filamentous fungus. The total activity of cellulolytic enzymes and protein concentration were significantly increased (1.1~1.2 times) in media containing Avicel 24-72 h after 2 and 5 min of plasma treatment. The mRNA levels of four cellulolytic enzymes in fungal hyphae grown in media with Avicel were significantly increased (1.3~17 times) 2-4 h after a 5 min of plasma treatment. The levels of intracellular NO and Ca2+ were increased in plasma-treated fungal hyphae grown in Avicel media after 48 h, and the removal of intracellular NO decreased the activity of cellulolytic enzymes in media and the level of vesicles in fungal hyphae. Our data suggest that plasma treatment can promote the transcription and secretion of cellulolytic enzymes into the culture media in the presence of Avicel (induction condition) by enhancing the intracellular level of NO and Ca2+.

Effect of Passage Number of Conditioned Medium Collected from Equine Amniotic Fluid Mesenchymal Stem Cells: Porcine Oocyte Maturation and Embryo Development.

Oocyte in vitro maturation (IVM) is the most important first step in in vitro embryo production. One prerequisite for the success of IVM in oocytes is to provide a rich culture microenvironment that meets the nutritional needs of developing oocytes. We applied different equine amniotic fluid mesenchymal stem cell conditioned medium (eAFMSC-CM) from passages 7, 18, and 27 to porcine oocytes during IVM to determine its effects on oocyte development and subsequent embryo development, specifically. The eAFMSC-CM from passage 7 (eAFMSC-CMp7) has a considerable impact on 9 genes: BAX, BCL2, SOD2, NRF2, TNFAIP6, PTGS2, HAS2, Cx37, and Cx43, which are associated with cumulus cell mediated oocyte maturation. GSH levels and distribution of mitochondrial and cortical granules were significantly increased in oocytes incubated with eAFMSC-CMp7. In addition, catalase and superoxide dismutase activities were high after IVM 44 h with eAFMSC-CMp7. After in vitro fertilization, blastocyst quality was significantly increased in the eAFMSC-CMp7 group compared to control. Lastly, the antioxidant effect of eAFMSC-CMp7 substantially regulated the expression of apoptosis, pluripotency related genes and decreased autophagy activity in blastocysts. Taken together, this study demonstrated that the eAFMSC-CMp7 enhanced the cytoplasmic maturation of oocytes and subsequent embryonic development by generating high antioxidant activity.

RAGE Inhibitors for Targeted Therapy of Cancer: A Comprehensive Review.

The receptor for advanced glycation end products (RAGE) is a member of the immunoglobulin family that is overexpressed in several cancers. RAGE is highly expressed in the lung, and its expression increases proportionally at the site of inflammation. This receptor can bind a variety of ligands, including advanced glycation end products, high mobility group box 1, S100 proteins, adhesion molecules, complement components, advanced lipoxidation end products, lipopolysaccharides, and other molecules that mediate cellular responses related to acute and chronic inflammation. RAGE serves as an important node for the initiation and stimulation of cell stress and growth signaling mechanisms that promote carcinogenesis, tumor propagation, and metastatic potential. In this review, we discuss different aspects of RAGE and its prominent ligands implicated in cancer pathogenesis and describe current findings that provide insights into the significant role played by RAGE in cancer. Cancer development can be hindered by inhibiting the interaction of RAGE with its ligands, and this could provide an effective strategy for cancer treatment.

Genetic localization of the orevactaene/epipyrone biosynthetic gene cluster in Epicoccum nigrum.

Epipyrone (EPN)-A (syn. orevactaene) is a polyketide compound of 3-d-galactosyl-4-hydroxy-2-pyrone with a modified heptaene acyl moiety, produced from Epicoccum nigrum and was reported to have various biological activities. Genome analysis identified a hypothetical EPN biosynthetic gene cluster (BGC) composed of the four genes epnABCD, which encode a highly-reducing fungal polyketide synthase, a glycosyltransferase, a cytochrome P450, and a transporter. The individual gene inactivation of epnABC resulted in the total loss of EPN production, while the inactivation of a nearby transcription factor-encoding gene had no effect on the production of EPN, substantiating that epnABCD is the EPN BGC. mRNA expression indicated no epnA transcription in the epnB knockout mutant and the occurrence of the bicistronic transcription of epnAB. This study defined an EPN BGC, which is the first blueprint reported for glycosylated 2-pyrone polyketide biosynthesis.

Efficacy of intermittent epidural dexamethasone bolus for zoster-associated pain beyond the acute phase.

Herpes zoster develops when latent varicella zoster virus is reactivated in the trigeminal or dorsal root ganglions. Zoster-associated pain (ZAP) is neuropathic pain caused by the herpes zoster virus. Histological studies of postherpetic neuralgia patients suggest that inflammation is involved in ZAP. The effectiveness of local anesthetic and steroid epidural injections in ZAP patients has been reported. However, most studies included patients with acute herpes zoster, and the safety and therapeutic effects of different doses of epidural steroids in ZAP patients remain elusive. In this study, we randomly assigned 42 patients with severe ZAP beyond the acute phase, as determined by a numeric rating scale (NRS) score ≥7, to receive continuous epidural infusion of local anesthetics with either a one-time 5-mg dose or intermittent repeated doses (15 mg total) of dexamethasone. We found that intermittent repeated epidural dexamethasone bolus resulted in reduced NRS scores and an increased likelihood of complete remission in ZAP patients without any adverse effects. Thus, our results suggest that intermittent repeated epidural dexamethasone administration is safe and effective for treatment of ZAP beyond the acute phase.

Effects of high voltage nanosecond pulsed plasma and micro DBD plasma on seed germination, growth development and physiological activities in spinach.

In this study, we analyzed seed germination, seedling growth, and physiological aspects after treatment with high voltage nanosecond pulsed plasma and micro DBD plasma in spinach (Spinacia oleracea L.), a green leafy vegetable known to have low germination rate. Both germination and dry weight of seedlings increased after high voltage pulse shots were applied to spinach seeds. However seeds treated with many shots (10 shots) showed a decrease in germination rate and seedling growth. Seeds treated with air DBD plasma exhibited slightly higher germination and subsequent seedling growth than those treated with N2 plasma. Seed surface was degenerated after treated with high voltage pulsed plasma and micro DBD plasma but no significant difference in the degree of degeneration was observed among micro DBD plasma treatment time. Level of GA3 hormone and mRNA expression of an amylolytic enzyme-related gene in seeds were elevated 1 day after treatment with high voltage pulsed plasma. The relative amount of chlorophyll and total polyphenols in spinach seedlings grown from seeds treated with air DBD plasma was increased in 30 s, 1 min, and 3 min treatments. Taken together, our results suggest a possibility that plasma can enhance seed germination by triggering biochemical processes in seeds.

Air atmospheric-pressure plasma-jet treatment enhances the attachment of human gingival fibroblasts for early peri-implant soft tissue seals on titanium dental implant abutments.

OBJECTIVE: Although dental implants are commonly used for tooth restoration, there is a lack of studies of treatment regimens for preventing extra-oral infection and decreasing osseointegration failures by establishing early peri-implant soft tissue seals on titanium dental implant abutments. In this study, air atmospheric-pressure plasma-jet (AAPPJ) treatment was applied to titanium disks to assay the potential for early peri-implant soft tissue seals on titanium dental implant abutment. MATERIALS AND METHODS: After titanium disks were treated with AAPPJ for 10 s at 250, 500, 1000 and 1500 sccm, surface analysis was performed; the control group received air only or no treatment. Human gingival fibroblasts (HGF) were seeded onto the specimens for evaluating cell attachment and proliferation and adherent-cell morphology was visualized via confocal microscopy. RESULTS: In AAPPJ-treated specimens, the water contact angle decreased according to increased flow rate. Oxygen composition increased in XPS, but no topographical changes were detected. The effect of AAPPJ treatment at 1000 sccm was apparent 2 mm from the treated spot, with a 20% increase in early cell attachment and proliferation. Adherent HGF on AAPPJ-treated specimens displayed a stretched phenotype with more vinculin formation than the control group. CONCLUSIONS: Within the limitations of this study, the results indicate that AAPPJ treatment may enhance the early attachment and proliferation of HGF for establishing early peri-implant soft tissue seals on titanium dental implant abutments with possible favorable effects of osseointegration of dental implant.

Carvacrol instigates intrinsic and extrinsic apoptosis with abrogation of cell cycle progression in cervical cancer cells: Inhibition of Hedgehog/GLI signaling cascade.

Recent times have seen a strong surge in therapeutically targeting the hedgehog (HH)/GLI signaling pathway in cervical cancer. HH signaling pathway is reported to be a crucial modulator of carcinogenesis in cervical cancer and is also associated with recurrence and development of chemoresistance. Moreover, our previous reports have established that carvacrol (CAR) inhibited the proliferation of prostate cancer cells via inhibiting the Notch signaling pathway and thus, it was rational to explore its antiproliferative effects in cervical cancer cell lines. Herein, the present study aimed to investigate the anticancer and apoptotic potential of CAR on C33A cervical cancer cells and further explore the underlying mechanisms. We found that CAR significantly suppressed the growth of C33A cells, induced cell cycle arrest, and enhanced programmed cell death along with augmentation in the level of ROS, dissipated mitochondrial membrane potential, activation of caspase cascade, and eventually inhibited the HH signaling cascade. In addition, CAR treatment increased the expression of pro-apoptotic proteins (Bax, Bad, Fas-L, TRAIL, FADDR, cytochrome c) and concomitantly reduced the expression of anti-apoptotic proteins (Bcl-2 and Bcl-xL) in C33A cells. CAR mediates the activation of caspase-9 and -3 (intrinsic pathway) and caspase-8 (extrinsic pathway) accompanied by the cleavage of PARP in cervical cancer cells. Thus, CAR induced apoptosis by both the intrinsic and extrinsic apoptotic pathways. CAR efficiently inhibited the growth of cervical cancer cells via arresting the cell cycle at G0/G1 phase and modulated the gene expression of related proteins (p21, p27, cyclin D1 and CDK4). Moreover, CAR inhibited the HH/GLI signaling pathway by down regulating the expression of SMO, PTCH and GLI1 proteins in cervical carcinoma cells. With evidence of the above results, our data revealed that CAR treatment suppressed the growth of HPV-C33A cervical cancer cells and further elucidated the mechanistic insights into the functioning of CAR.

Development of Dementia in Type 2 Diabetes Patients: Mechanisms of Insulin Resistance and Antidiabetic Drug Development.

Dementia is reported to be common in those with type 2 diabetes mellitus. Type 2 diabetes contributes to common molecular mechanisms and an underlying pathology with dementia. Brain cells becoming resistant to insulin leads to elevated blood glucose levels, impaired synaptic plasticity, microglial overactivation, mitochondrial dysfunction, neuronal apoptosis, nutrient deprivation, TAU (Tubulin-Associated Unit) phosphorylation, and cholinergic dysfunction. If insulin has neuroprotective properties, insulin resistance may interfere with those properties. Risk factors have a significant impact on the development of diseases, such as diabetes, obesity, stroke, and other conditions. Analysis of risk factors of importance for the association between diabetes and dementia is important because they may impede clinical management and early diagnosis. We discuss the pathological and physiological mechanisms behind the association between Type 2 diabetes mellitus and dementia, such as insulin resistance, insulin signaling, and sporadic forms of dementia; the relationship between insulin receptor activation and TAU phosphorylation; dementia and mRNA expression and downregulation of related receptors; neural modulation due to insulin secretion and glucose homeostasis; and neuronal apoptosis due to insulin resistance and Type 2 diabetes mellitus. Addressing these factors will offer clinical outcome-based insights into the mechanisms and connection between patients with type 2 diabetes and cognitive impairment. Furthermore, we will explore the role of brain insulin resistance and evidence for anti-diabetic drugs in the prevention of dementia risk in type 2 diabetes.

CRISPR/Cas9 based genome editing for targeted transcriptional control in triple-negative breast cancer.

Breast cancer (BC) is the most common type of cancer in women at the global level and the highest mortality rate has been observed with triple-negative breast cancer (TNBC). Accumulation of genetic lesions an aberrant gene expression and protein degradation are considered to underlie the onset of tumorigenesis and metastasis. Therefore, the challenge to identify the genes and molecules that could be potentially used as potent biomarkers for personalized medicine against TNBC with minimal or no associated side effects. Discovery of the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR associated protein 9 (Cas9) arrangement and an increasing repertoire of its new variants has provided a much-needed fillip towards editing TNBC genomes. In this review, we discuss the CRISPR/Cas9 genome editing, CRISPR Technology for diagnosis of (Triple-negative breast cancer) TNBC, Drug Resistance, and potential applications of CRISPR/Cas9 and its variants in deciphering or engineering intricate molecular and epigenetic mechanisms associated with TNBC. Furthermore, we have also explored the TNBC and CRISPR/Cas9 genome editing potential for repairing, genetic modifications in TNBC.

Effects of Pre-Treatment Using Plasma on the Antibacterial Activity of Mushroom Surfaces.

Although non-thermal atmospheric pressure plasma is an efficient tool for preventing post-harvest microbial contamination, many studies have focused on the post-treatment of infected or contaminated foods. In this study, we examined the antimicrobial quality of mushrooms pre-treated with a non-thermal atmospheric pressure plasma jet (NTAPPJ) or plasma-treated water (PTW). The CFU (Colony Forming Unit) number of Escherichia coli inoculated on surfaces of mushrooms pre-treated with NTAPPJ or PTW was significantly reduced (about 60-75% for NTAPPJ and about 35-85% for PTW), and the reduction rate was proportional to the treatment time. Bacterial attachment and viability of the attached bacteria were decreased on NTAPPJ-treated mushroom surfaces. This may be caused by the increased hydrophilicity and oxidizing capacity observed on NTAPPJ-treated mushroom surfaces. In PTW-treated mushrooms, bacterial attachment was not significantly changed, but death and lipid peroxidation of the attached bacteria were significantly increased. Analysis of mushroom quality showed that loss of water content was greater in mushrooms treated with NTAPPJ compared to that in those with no treatment (control) and PTW treatment during storage. Our results suggest that pre-treatment with NTAPPJ or PTW can improve the antibacterial quality of mushroom surfaces by decreasing bacterial attachment (for NTAPPJ) and increasing bacterial lipid peroxidation (for both NTAPPJ and PTW).

Electric-field-induced electroporation and permeation of reactive oxygen species across a skin membrane.

Electroporation processes affect the permeability of cell membranes, which can be utilized for the delivery of plasma species in cancer therapy. By means of computational dynamics, many aspects of membrane electroporation have been unveiled at the atomic level for lipid membranes. Herein, a molecular dynamics simulation study was performed on native and oxidized membrane systems with transversal electric fields. The simulation result shows that the applied electric field mainly affects the membrane properties so that electroporation takes place and these pores are lined by hydrophilic headgroups of the lipid components. The calculated hydrophobic thickness, lateral diffusion and pair correlation revealed the role of 5α-CH in creation of water-pore in an oxidized membrane. Additionally, the permeability of reactive oxygen species was examined through these electroporated systems. The permeability study suggested that water pores in the membrane facilitate the penetration of these species across the membrane to the interior of the cell. These findings may have significance in experimental applications in vivo as once the reactive oxygen species reaches the interior of the cell, they may cause oxidative stress and induce apoptosis.Communicated by Ramaswamy H. Sarma.

Current Potential Therapeutic Approaches against SARS-CoV-2: A Review.

The ongoing SARS-CoV-2 pandemic is a serious threat to public health worldwide and, to date, no effective treatment is available. Thus, we herein review the pharmaceutical approaches to SARS-CoV-2 infection treatment. Numerous candidate medicines that can prevent SARS-CoV-2 infection and replication have been proposed. These medicines include inhibitors of serine protease TMPRSS2 and angiotensin converting enzyme 2 (ACE2). The S protein of SARS-CoV-2 binds to the receptor in host cells. ACE2 inhibitors block TMPRSS2 and S protein priming, thus preventing SARS-CoV-2 entry to host cells. Moreover, antiviral medicines (including the nucleotide analogue remdesivir, the HIV protease inhibitors lopinavir and ritonavir, and wide-spectrum antiviral antibiotics arbidol and favipiravir) have been shown to reduce the dissemination of SARS-CoV-2 as well as morbidity and mortality associated with COVID-19.

Clinical and microbiological effects of adjunctive local delivery of minocycline (Periocline®) in patients receiving supportive periodontal therapy: a pilot study.

PURPOSE: This study aimed to evaluate the clinical and microbiological efficacy of adjunctive local delivery of minocycline (Periocline®) in patients receiving supportive periodontal therapy (SPT) after initial treatment. METHODS: The participants were 16 men and 8 women (age, 20-65 years) who had at least 15 natural teeth, underwent SPT for more than 1 year due to chronic periodontitis, had 4 or more periodontal pocket sites deeper than 5 mm, and showed >25% gingival bleeding on probing (BoP). They were randomly assigned to the test and control groups. In the test group, mechanical debridement and local antibiotic delivery were performed for all periodontal sulci/pockets; in the control group, mechanical debridement and saline irrigation were performed. In patients who underwent SPT for more than 1 year, clinical and microbiological examinations were performed at baseline and 1 and 3 months after SPT. The clinical examination included an assessment of the periodontal pocket depth, clinical attachment level, plaque index, and BoP. Microbial tests were performed using real-time polymerase chain reaction; the relative ratios of Porphyromonas gingivalis and Fusobacterium nucleatum were determined. RESULTS: Both groups showed significant improvements in clinical parameters at 1 and 3 months from baseline; there were no significant changes between months 1 and 3. Intergroup differences were insignificant. The microbiological analysis revealed no significant differences in P. gingivalis and F. nucleatum ratios across time points. While intergroup differences were insignificant, there was a tendency for the P. gingivalis and F. nucleatum ratios to decrease in the test group. CONCLUSIONS: Mechanical debridement in patients receiving maintenance therapy resulted in clinically significant improvement; the effectiveness of additional local delivery of antibiotics was not significant. The ratios of P. gingivalis and F. nucleatum showed a tendency to decrease in the test group, although it was not significant.

Plasma-mediated enhancement of enzyme secretion in Aspergillus oryzae.

Technical bottlenecks in protein production and secretion often limit the efficient and robust industrial use of microbial enzymes. The potential of non-thermal atmospheric pressure plasma to overcome these technical barriers was examined. Spores of the fermenting fungus Aspergillus oryzae (A. oryzae) were submerged in potato dextrose broth (PDB) (5 × 106 per ml) and treated with micro dielectric barrier discharge plasma at an input voltage of 1.2 kV and current of 50 to 63 mA using nitrogen as the feed gas. The specific activity of α-amylase in the broth was increased by 7.4 to 9.3% after 24 and 48 h of plasma treatment. Long-lived species, such as NO2 - and NO3 - , generated in PDB after plasma treatment may have contributed to the elevated secretion of α-amylase. Observations after 24 h of plasma treatment also included increased accumulation of vesicles at the hyphal tip, hyphal membrane depolarization and higher intracellular Ca2+ levels. These results suggest that long-lived nitrogen species generated in PDB after plasma treatment can enhance the secretion of α-amylase from fungal hyphae by depolarizing the cell membrane and activating Ca2+ influx into hyphal cells, eventually leading to the accumulation of secretory vesicles near the hyphal tips.

Drug Resistance Reversal Potential of Nanoparticles/Nanocomposites via Antibiotic's Potentiation in Multi Drug Resistant P. aeruginosa.

Bacteria employ numerous resistance mechanisms against structurally distinct drugs by the process of multidrug resistance. A study was planned to discover the antibacterial potential of a graphene oxide nanosheet (GO), a graphene oxide-zinc oxide nanocomposite (GO/ZnO), a graphene oxide-chitosan nanocomposite (GO-CS), a zinc oxide decorated graphene oxide-chitosan nanocomposite (GO-CS/ZnO), and zinc oxide nanoparticles (ZnO) alone and in a blend with antibiotics against a PS-2 isolate of Pseudomonas aeruginosa. These nanocomposites reduced the MIC of tetracycline (TET) from 16 folds to 64 folds against a multidrug-resistant clinical isolate. Efflux pumps were interfered, as evident by an ethidium bromide synergy study with nanocomposites, as well as inhibiting biofilm synthesis. These nanoparticles/nanocomposites also decreased the mutant prevention concentration (MPC) of TET. To the best of our knowledge, this is the first report on nanomaterials as a synergistic agent via inhibition of efflux and biofilm synthesis.

Description of two new Proceroecia species (Ostracoda: Halocyprididae) from neritic waters off South Korea with an insight into the morphological and molecular diversity of the genus.

Two new planktonic ostracods of the genus Proceroecia Kock, 1992, P. hwanghaensis sp. nov. and P. joseondonghaensis sp. nov., collected from neritic waters off the south coast of South Korea are described. Morphologically, they are similar to P. microprocera (Angel, 1971), the type species of the genus, but show several clear morphological differences, most prominent being the shape of the male endopodite on the second antenna and the presence of a sensilla on the coxale of the fifth limb. The two new species have subtle differences, such as the length of the frontal organ, number of spines on the comb-like e-seta on the first antenna in males, number of spinules on the b-seta on the second antenna in females, etc. Sequences derived from partial mitochondrial cytochrome oxidase c subunit 1 (mtCOI) for these novel species have been compared with sequences available for other Proceroecia species on GenBank, including P. microprocera. These comparisons suggest that both new species are distinct taxa. They also indicate that one set of sequences on GeneBank previously attributed to P. microprocera and derived from material collected from Chinese waters, belong to P. hwanghaensis, and that another set of sequences of an unidentified Proceroecia species from the South China Sea can be attributable to P. joseondonghaensis. Hence, these new species occur widely in the neritic waters of East Asia. The present study increases the number of the known Proceroecia species to nine, and the numbers of halocyprid ostracod species recorded from Korean waters to six.

Immunopathology, host-virus genome interactions, and effective vaccine development in SARS-CoV-2.

Coronaviruses are a group of enveloped RNA viruses that are diversely found in humans and now declared a global pandemic by the World Health Organization in March 2020. The population's susceptibility to these highly pathogenic coronaviruses has contributed to large outbreaks, evolved into public health events, and rapidly transmitted globally. Thus, there is an urgent need to develop effective therapies and vaccines against this disease. In the primary stage of severe acute respiratory syndrome coronavirus (SARS-COV-2) infection, the signs and symptoms are nonspecific, and many more cases have been observed than initially expected. Genome sequencing is performed regularly to identify genetic changes to SARS-COV-2, and vaccine development is focused on manufacture, production, and based on specific problems, and very few are available on recent developments in the prevention of outbreaks. The aim of this review article to explore recent updates on SARS-COV-2 in the context of pathogenesis during disease progression, and innate acquired mechanisms of defense, This includes advances in diagnostics, susceptibility, and severity of host-virus genome interactions, modes of transmission, active compounds being used in pre-clinical and clinical trials for the treatment of patients, vaccine developments, and the effectiveness of SARS-COV-2 prevention and control measures. We have summarized the importance of pathophysiology immune response, Diagnostics, vaccine development currently approaches explored for SARS-COV-2.

Computational Modeling on Aquaporin-3 as Skin Cancer Target: A Virtual Screening Study.

Aquaporin-3 (AQP3) is one of the aquaglyceroporins, which is expressed in the basolateral layer of the skin membrane. Studies have reported that human skin squamous cell carcinoma overexpresses AQP3 and inhibition of its function may alleviate skin tumorigenesis. In the present study, we have applied a virtual screening method that encompasses filters for physicochemical properties and molecular docking to select potential hit compounds that bind to the Aquaporin-3 protein. Based on molecular docking results, the top 20 hit compounds were analyzed for stability in the binding pocket using unconstrained molecular dynamics simulations and further evaluated for binding free energy. Furthermore, examined the ligand-unbinding pathway of the inhibitor from its bound form to explore possible routes for inhibitor approach to the ligand-binding site. With a good docking score, stability in the binding pocket, and free energy of binding, these hit compounds can be developed as Aquaporin-3 inhibitors in the near future.