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Omicron, another SARS-CoV-2 variant, has been recorded and reported as a VoC. It has already spread across >30 countries and is a highly mutated variant. We tried to understand the role of mutations in the investigated variants by comparison with previous characterized VoC. We have mapped the mutations in Omicron S-glycoprotein's secondary and tertiary structure landscape using bioinformatics tools and statistical software and developed different models. In addition, we analyzed the effect of diverse mutations in antibody binding regions of the S-glycoprotein on the binding affinity of the investigated antibodies. This study has chosen eight significant mutations in Omicron (D614G, E484A, N501Y, Q493K, K417N, S477N, Y505H G496S), and seven of them are located in the RBD region. We also performed a comparative analysis of the ΔΔG score of these mutations to understand the stabilizing or destabilizing properties of the investigated mutations. The analysis outcome shows that D614G, Q493K, and S477N mutations are stable mutations with ΔΔG scores of 0.351 kcal/mol, 0.470 kcal/mol, and 0.628 kcal/mol, respectively, according to DynaMut estimations. While other mutations (E484A, N501Y, K417N, Y505H, G496S) showed destabilizing results. The D614G, E484A, N501Y, K417N, Y505H, and G496S mutations increased the molecular flexibility of S-glycoprotein to interact with the ACE2 receptor, increasing the variant's infectivity. Our study will contribute to research on the SARS-CoV-2 variant, Omicron, by providing information on the mutational pattern and exciting properties of these eight significant mutations, such as antibody escape and infectivity quotient (stabilizing or destabilizing; increased or decreased molecular flexibility of S-glycoprotein to interact with the human ACE2 receptor). [ABSTRACT FROM AUTHOR]

During the COVID-19 pandemic, one of the biggest challenges was the continuous evolution of SARS-CoV-2 through various mutations. This has resulted in the emergence of several variants and subvariants. The escape mutations are reported as significant mutations in several variants and subvariants responsible for immune, antibody, and nAb escape. It has been reported that FLip mutations (L455F and F456L) in the spike RBD are responsible for immune evasion and antibody escape. Recently, WHO has included a new SARS-CoV-2 VOI, JN.1 lineage, a descendent of BA.2.86. The variant is reported from more than 41 countries, including France, the USA, Canada, the UK, Singapore, Sweden, and India. It contains FLip mutations in the spike protein in RBD (L455F and F456L). The risk assessment of the variant by WHO shows it has increased transmission, immune escape, and antibody escape due to the mutations. The article illustrated that FLip mutations in RBD (L455F and F456L) are responsible for augmented transmission and immune and antibody escape. [ABSTRACT FROM AUTHOR]

Several clinical trials started during the COVID-19 pandemic to discover effective therapeutics led to identify a few candidates from the major clinical trials. However, in the past several months, quite a few SARS-CoV-2 variants have emerged with significant mutations. Major mutations in the S-glycoprotein and other parts of the genome have led to the antibody's escape to small molecule-based therapeutic resistance. The mutations in S-glycoprotein trigger the antibody escape/resistance, and mutations in RdRp might cause remdesivir resistance. The article illustrates emerging mutations that have resulted in antibody escape to therapeutics resistance. In this direction, the article illustrates presently developed neutralizing antibodies (with their preclinical, clinical stages) and antibody escapes and associated mutations. Finally, owing to the RdRp mutations, the antiviral small molecules resistance is illustrated. [ABSTRACT FROM AUTHOR]

The Ebola virus disease is a deadly pathogenic disease caused by the Ebola virus. It has been observed that this disease causes a high case-fatality rate. Several species of this virus were detected from the genus Ebola virus. Among them, four species of this virus (Ebola, Taï Forest, Sudan, and Bundibugyo) caused disease in humans. Scientists are now focusing on the various therapeutic developments for the treatment of this disease. This article has attempted to depict the development of the entire therapeutic scenario of this disease. In addition, the article tried to illustrate the developmental strategy of the different therapeutics such as small-molecule inhibitors, small interfering RNAs, antibodies, ion channel inhibitors, interferons, and combination therapy against Ebola virus disease. Presently, two monoclonal antibodies (REGN-EB3 and mAb114) showed better efficacy in the Pamoja tuLinde Maisha trial and received approval from the United States Food and Drug Administration. However, scientists should focus on developing more economic therapeutics. [ABSTRACT FROM AUTHOR]

• We discussed immunoinformatics approaches for SARS-CoV-2 vaccine development. • Different topics such as T cell and B cell epitopes, their identification and characterization for vaccine development against SARS-CoV-2 were discussed. • We also summarize a variety of infectious pathogens and diseases where immunoinformatics studies were applied. • Different immunoinformatics tools were enlisted for SARS-CoV-2 vaccine development. Presently, immunoinformatics is playing a significant role in epitope identification and vaccine designing for various critical diseases. Using immunoinformatics, several scientists are trying to identify and characterize T cell and B cell epitopes as well as design peptide-based vaccine against SARS-CoV-2. In this review article, we have tried to discuss the importance in adaptive immunity and its significance for designing the SARS-CoV-2 vaccine. Moreover, we have attempted to illustrate several significant key points for utilizing immunoinformatics for vaccine designing, such as the criteria for selection and identification of epitopes, T cell epitope, and B cell epitope prediction and different emerging tools/databases for immunoinformatics. In the current scenario, a few immunoinformatics studies have been performed for various infectious pathogens and related diseases. Thus, we have also summarized and included these current immunoinformatics studies in this review article. Finally, we have discussed about the probable T cell and B cell epitopes and their identification and characterization for vaccine designing against SARS-CoV-2. [ABSTRACT FROM AUTHOR]

miRNAs, a class of small endogenous RNAs, are one of the essential biopharmaceuticals which are in commercial spans as next-generation medicine in recent times. A snapshot of the current scenario regarding the miRNAs as biopharmaceuticals have been discussed. In this work, biopharmaceutical companies working with miRNAs and the current status of preclinical/clinical trials about miRNA therapeutics have been reviewed. Finally, recent updates on the absorption, distribution, metabolism, and excretion (ADME), as well as a delivery system of miRNAs, have been illustrated. [ABSTRACT FROM AUTHOR]

The COVID-19 outbreak is a disaster now throughout the world. To stop this outbreak, we appeal through the paper for extensive partnership, collaboration and teamwork among the all levels of workers such as scientist, doctors, medical professionals, social workers, policy makers, governments, pharmaceutical firms, funding aid agencies to stop the pandemic immediately. [ABSTRACT FROM AUTHOR]

• Recently, the emergence of MPX has created a global threat, and vaccination is one of the significant ways to fight against the virus. • The article describes the important points and issues for vaccines and vaccinations related to the MPXV. • It also illustrates significant research on the MPXV, especially smallpox vaccines, and its outcome in MPX infection. • Vaccination preparedness has been illustrated in various countries like the USA, UK, Canada, Denmark, Germany, etc. The recent emergence of monkeypox (MPX) has created a global threat. The number of infected and suspected cases of MPX is increasing in different parts of the world, especially in non-African countries. However, vaccines are available to fight against this disease. It has been observed that smallpox vaccines can be used to protect against MPX. The present article highlights the significant points and various issues for vaccines and vaccinations that should be considered related to MPX. This paper illustrates current vaccines for smallpox that can be utilized to protect against MPX infection. The article also describes the different significant research on MPXV, especially smallpox vaccines, and its outcome in MPX infection. We have also tried to depict the smallpox vaccination eradication model through the statistical interface using smallpox eradication data from Central and West Africa between 1967 and 1972. We suggest that these models might be helpful for the eradication of MPX in the middle to low-economic countries. Simultaneously, we have also discussed vaccination preparedness in different countries like the USA, UK, Canada, Denmark, Germany, etc. Our report might be helpful to scientists and policymakers in understanding the vaccines and vaccination against MPX and formulating effective strategies to fight against the disease. [ABSTRACT FROM AUTHOR]

The massive increase in COVID-19 infection had generated a second wave in India during May–June 2021 with a critical pandemic situation. The Delta variant (B.1.617.2) was a significant factor during the second wave. Conversely, the UK had passed through the crucial phase of the pandemic from November to December 2020 due to B.1.1.7. The study tried to comprehend the pandemic response in the UK and India to the spread of the B.1.1.7 (Alpha, UK) variant and B.1.617.2 (Delta, India) variant. This study was performed in three directions to understand the pandemic response of the two emerging variants. First, we served comparative genomics, such as genome sequence submission patterns, mutational landscapes, and structural landscapes of significant mutations (N501Y, D614G, L452R, E484Q, and P681R). Second, we performed evolutionary epidemiology using molecular phylogenetics, scatter plots of the cluster evaluation, country-wise transmission pattern, and frequency pattern. Third, the receptor binding pattern was analyzed using the Wuhan reference strain and the other two variants. The study analyzed the country-wise and region-wise genome sequences and their submission pattern, molecular phylogenetics, scatter plot of the cluster evaluation, country-wise geographical distribution and transmission pattern, frequency pattern, entropy diversity, and mutational landscape of the two variants. The structural pattern was analyzed in the N501Y, D614G L452R, E484Q, and P681R mutations. The study found increased molecular interactivity between hACE2-RBD binding of B.1.1.7 and B.1.617.2 compared to the Wuhan reference strain. Our receptor binding analysis showed a similar indication pattern for hACE2-RBD of these two variants. However, B.1.617.2 offers slightly better stability in the hACE2-RBD binding pattern through MD simulation than B.1.1.7. The increased hACE2-RBD binding pattern of B.1.1.7 and B.1.617.2 might help to increase the infectivity compared to the Wuhan reference strain. [Display omitted] • Comparative genomics of two emerging SARS-CoV-2 variants (B.1.1.7 and B. 1.617.2). • Evolutionary epidemiology, geographical distribution and country-wise transmission patterns of study of Alpha.1.1.7 and Delta. 1.617.2. • Landscape of significant mutations such as L452R, E484Q, N501Y, D614G and P681R. • RBD-hACE2 receptor binding pattern analysis in B.1.1.7 and B. 1.617.2 compare to Wuhan reference strain. [ABSTRACT FROM AUTHOR]

Abstract: Using computational biology, we have depicted the insulin phylogenetics. We have also analyzed the sequence alignment and sequence logos formation for both the insulin chain A and B for three groups namely, the mammalian group, vertebrates group and fish group. We have also analyzed cladograms of insulin for the mammalian group. In accordance with that path lengths, matrix for distance analysis, matching representation of nodes of the cladogram and dissimilarity between two nodes have been performed for both of the A and B chains of the mammalian group. Our results show that 12 amino acid residues (GlyA1, IleA2, ValA3, TyrA19, CysA20, AsnA21, LeuB6, GlyB8, LeuB11, ValB12, GlyB23 and PheB24) are highly conserved for all groups and among them some (GlyA1, IleA2, ValA3);(TyrA19, CysA20, AsnA21) are continuous. This study shows a rapid method to calculate the amino acid sequences in terms of evolutionary conservation rates as well as molecular phylogenetics. [Copyright &y& Elsevier]

Abstract: India''s biotechnology industry has been growing towards new heights in conjunction with the recent economic outburst. The country has the potential to revolutionize biopharmaceutical and healthcare sectors. In this review, we have highlighted the achievements of India''s biotechnology industry, especially biopharmaceutical and healthcare sectors that include therapeutics, diagnostics, stem cell research, human healthcare related bioinformatics and animal health care. We have also described regulatory mechanisms involved in India''s health care biotech including manpower development. [Copyright &y& Elsevier]

In recent years, a total of seven human pathogenic coronaviruses (HCoVs) strains were identified, i.e., SARS-CoV, SARS-CoV-2, MERS-CoV, HCoV-OC43, HCoV-229E, HCoV-NL63, and HCoV-HKU1. Here, we performed an analysis of the protease recognition sites and antigenic variation of the S-protein of these HCoVs. We showed tissue-specific expression pattern, functions, and a number of recognition sites of proteases in S-proteins from seven strains of HCoVs. In the case of SARS-CoV-2, we found two new protease recognition sites, each of calpain-2, pepsin-A, and caspase-8, and one new protease recognition site each of caspase-6, caspase-3, and furin. Our antigenic mapping study of the S-protein of these HCoVs showed that the SARS-CoV-2 virus strain has the most potent antigenic epitopes (highest antigenicity score with maximum numbers of epitope regions). Additionally, the other six strains of HCoVs show common antigenic epitopes (both B-cell and T-cell), with low antigenicity scores compared to SARS-CoV-2. We suggest that the molecular evolution of structural proteins of human CoV can be classified, such as (i) HCoV-NL63 and HCoV-229E, (ii) SARS-CoV-2, and SARS-CoV and (iii) HCoV-OC43 and HCoV-HKU1. In conclusion, we can presume that our study might help to prepare the interventions for the possible HCoVs outbreaks in the future. • Analysis of the protease recognition sites and antigenic variation of S-protein of seven HCoVs. • Tissue specific- expression pattern analysis of the proteases of seven HCoVs. • Grouping of seven HCoVs strains through molecular phylogenetics using of S, M, E, N proteins. • Immunogenicity and conservancy analysis of common B-cell and T-cell epitopes of seven HCoVs. [ABSTRACT FROM AUTHOR]

The transdermal drug delivery system is an exceptionally safe and well-tolerable therapeutic approach that has immense potential for delivering active components against bone-related pathologies. However, its use is limited in the current clinical practices due to the low skin permeability of most active drugs in the formulation. Thus, innovations in the methodologies of skin permeation enhancement techniques are suggested to overcome this limitation. Although various transdermal drug delivery systems are studied to date, there are insufficient studies comparing the therapeutic efficacy of transdermal delivery systems to oral delivery systems. Thus, creating a decision-making dilemma between oral or transdermal therapies. Therefore, a timely review is inevitable to develop a platform for future researchers to develop next-generation transdermal drug delivery strategies against skeletal diseases that must be convenient and cost-effective for the patients with improved therapeutic efficacy. Here, we will outline the most recent strategies that can overcome the choice limitation of the drug and enhance the transdermal adsorption of various types of drugs to treat bone disorders. For the first time, in this review paper, we will highlight the preclinical and clinical studies on the different transdermal delivery methods. Thus, providing insight into the current therapeutic approaches and suggesting new directions for the advancements in transdermal drug delivery systems against bone disorders. [Display omitted] [ABSTRACT FROM AUTHOR]

In the last two years, the world encountered the SARS-CoV-2 virus, which is still dominating the population due to the absence of a viable treatment. To eradicate the global pandemic, scientists, doctors, and researchers took an exceptionally significant initiative towards the development of effective therapeutics to save many lifes. This review discusses about the single-domain antibodies (sdAbs), also called nanobodies, their structure, and their types against the infections of dreadful SARS-CoV-2 virus. A precise description highlights the nanobodies and their therapeutic application against the other selected viruses. It aims to focus on the extraordinary features of these antibodies compared to the conventional therapeutics like mAbs, convalescent plasma therapy, and vaccines. The stable structure of these nanobodies along with the suitable mechanism of action also confers greater resistance to the evolving variants with numerous mutations. The nanobodies developed against SARS-CoV-2 and its mutant variants have shown the greater neutralization potential than the primitive ones. Engineering of these specialized antibodies by modern biotechnological approaches will surely be more beneficial in treating this COVID-19 pandemic along with certain other viral infections. [ABSTRACT FROM AUTHOR]

• The article highlighted an overview of long COVID, significant clinical symptoms, and different long COVID clinical trials. • It illustrated different challenges and recommendations for long COVID. • The article depicted the underlying mechanisms and risk factors of long COVID. • The ongoing clinical trials that might provide future therapeutics for treating long COVID, were also highlighted. Long COVID was reported as a multi-systemic condition after the infection of SARS-CoV-2, and more than 65 million people are suffering from this disease. It has been noted that around 10% of severe SARS-CoV-2 infected individuals are suffering from the enduring effects of long COVID. The symptoms of long COVID have also been noted in several mild or asymptomatic SARS-CoV-2 infected individuals. While limited reports on clinical trials investigating new therapeutics for long COVID exist, there is an abundance of scattered information available regarding these trials. This review explores the extensive literature search, and complete clinical trial database search to map the current status of long COVID clinical trials worldwide. The study listed about 110 long COVID clinical trials. In addition to conducting extensive long COVID clinical trials, we have comprehensively presented an overview of the condition, its symptoms, notable manifestations, associated clinical trials, the unique challenges it poses, and our recommendations for addressing long COVID. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract The blood brain barrier (BBB) offers protection to the central nervous system (CNS) by maintaining homeostasis. Besides restricting the entry of harmful xenobiotics and endogenous molecules to CNS, BBB also limits the entry of therapeutic agents. Nanotechnology offers the possibility to deliver small molecules/drugs against CNS disorders across BBB. Recently, due to excellent biocompatibility, functional versatility and unique surface electrostatics properties nanodiamonds are also being explored for their drug delivery potential against BBB. Although, studies has been done to understand the mechanisms involved in drug delivery across BBB, but still, progress in the development of any functional drug delivery systems across BBB is in juvenile stages. For this purpose, the strategic developments of more potent drug delivery systems to CNS via endocytic pathways appears to be the most promising approach. Endocytic pathways are essential for communication and transport of nutrients across BBB in endothelial cells. Moreover, modifications of the nanotherapeutic agents with specific brain capillary endothelial cells targeting molecules or ligands have recently shown impressive results of successful delivery of drugs to the brain via receptor-mediated transcytosis. The current review provides a comprehensive insight in the advancements made in nanocarriers-based successful drug delivery to the CNS and their availability in clinics. [ABSTRACT FROM AUTHOR]

Emerging SARS-CoV-2 variants and subvariants are great concerns for their significant mutations, which are also responsible for vaccine escape. Therefore, the study was undertaken to develop a mutation-proof, next-generation vaccine to protect against all upcoming SARS-CoV-2 variants. We used advanced computational and bioinformatics approaches to develop a multi-epitopic vaccine, especially the AI model for mutation selection and machine learning (ML) strategies for immune simulation. AI enabled and the top-ranked antigenic selection approaches were used to select nine mutations from 835 RBD mutations. We selected twelve common antigenic B cell and T cell epitopes (CTL and HTL) containing the nine RBD mutations and joined them with the adjuvants, PADRE sequence, and suitable linkers. The constructs' binding affinity was confirmed through docking with TLR4/MD2 complex and showed significant binding free energy (−96.67 kcal mol−1) with positive binding affinity. Similarly, the calculated eigenvalue (2.428517e-05) from the NMA of the complex reveals proper molecular motion and superior residues' flexibility. Immune simulation shows that the candidate can induce a robust immune response. The designed mutation-proof, multi-epitopic vaccine could be a remarkable candidate for upcoming SARS-CoV-2 variants and subvariants. The study method might guide researchers in developing AI-ML and immunoinformatics-based vaccines for infectious disease. [ABSTRACT FROM AUTHOR]

Presently, we need more therapeutic molecules for this COVID-19 outbreak. The severity and mortality of the disease is associated with a high level of release of cytokine in the patients which is known as CRS (cytokine release syndrome) or cytokine storm syndrome. IL-6 is a type of pro-inflammatory cytokine which release in the severe COVID-19 patients. This cytokine initiates CRS the JAK-STAT or MAPK/NF-κB-IL-6 pathway. Tocilizumab, a humanized monoclonal antibody, is designed to bind both mIL-6R (membrane bound receptor for IL-6) and sIL-6R (soluble receptor for IL-6) and inhibit the JAK-STAT or MAPK/NF-κB-IL-6 signaling pathway. It finally stops the cytokine storm syndrome. However, we need to understand that how tocilizumab is bound with mIL-6R or sIL-6R. Similarly, we also need to understand more about the real molecular mechanism of activity of tocilizumab. [ABSTRACT FROM AUTHOR]

PLK-1 is a key player in the eukaryotic cell cycle. Cell cycle progression is precisely controlled by cell cycle regulatory kinases. PLK-1 is a mitotic kinase that actively regulates the G2/M transition, mitosis, mitotic exit, and cytokinesis. During cell cycle progression, PLK-1 controls various events related to the cell cycle maturation, directly and/or indirectly. On the contrary, aberrant expression of PLK-1 is strongly associated with tumorigenesis and its poor prognosis. The misexpression of PLK-1 causes the abnormalities including aneuploidy, mitotic defects, leading to tumorigenesis through inhibiting the p53 and pRB genes. Therefore, we reviewed the role of PLK-1 in the cell cycle progression and in the tumorigenesis either as a cell cycle regulator or on an attractive anti-cancer drug target. [ABSTRACT FROM AUTHOR]

• Hybrid immunity is the robust immunity that can provide the strongest possible protection against the SARS-CoV-2. • The components of hybrid immunity are antibodies, memory B cells, CD4+ T, and CD8+ T cells. • The study describes an overall view of hybrid immunity, the hybrid immunity in different countries, hybrid immunity and different SARS-CoV-2 variants, the molecular basis of hybrid immunity. • The study found that hybrid immunity in Indian Individuals might cause a less severe third wave in this country. Hybrid immunity has been accepted as the most robust immunity to fight against SARS-CoV-2. The hybrid immunity against the virus is produced in individuals who have contracted the disease and received the COVID-19 vaccine. This happens due to the cumulative effect of natural and acquired (vaccine) immunity, which provides higher antibody responses compared to natural and vaccine-produced immunity alone. Scientists have noted that it provides about 25 to 100 times higher antibody responses than natural and vaccine-produced immunity alone. Here, we have tried to illustrate the molecular basis of hybrid immunity against various SARS-CoV-2 variants. We have described hybrid immunity under different headings, which are as follows: an overview of hybrid immunity; a comparison between herd immunity and hybrid immunity against SARS-CoV-2; hybrid immunity in different countries; hybrid immunity and different SARS-CoV-2 variants; the molecular basis of hybrid immunity; and hybrid immunity in Indian scenario. India's large population has recovered from SARS-CoV-2, and data shows that over 1000 million of the population received at least one dose of the vaccine. Besides, many infected individuals who have recovered also received at least one dose of the vaccine leading to hybrid immunity with a less severe third wave compared to the first and second waves. Based on the available data, we hypothesize that people's hybrid immunity could be a major cause of the less severe third wave. [ABSTRACT FROM AUTHOR]

Leprosy is a significant universal health problem that is remarkably still a concern in developing countries due to infection frequency. New therapeutic molecules and next-generation vaccines are urgently needed to accelerate the leprosy-free world. In this direction, the present study was performed using two routes: proteome-mediated therapeutic target identification and mapping as well as multi-epitopic peptide-based novel vaccine development using state of the art of computational biology for the TN strain of M. leprae. The TN strain was selected from 65 Mycobacterium strains, and TN strain proteome mediated 83 therapeutic protein targets were mapped and characterized according to subcellular localization. Also, drug molecules were mapped with respect to protein targets localization. The Druggability potential of proteins was also evaluated. For multi-epitope peptide-based vaccine development, the four common types of B and T cell epitopes were identified (SLFQSHNRK, VVGIGQHAA, MMHRSPRTR, LGVDQTQPV) and combined with the suitable peptide linker. The vaccine component had an acceptable protective antigenic score (0.9751). The molecular docking of vaccine components with TLR4/MD2 complex exhibited a low ACE value (−244.12) which signifies the proper binding between the two molecules. The estimated free Gibbs binding energy ensured accurate protein-protein interactions (−112.46 kcal/mol). The vaccine was evaluated through adaptive immunity stimulation as well as immune interactions. The molecular dynamic simulation was carried out by using CHARMM topology-based parameters to minimize the docked complex. Subsequently, the Normal Mode Analysis in the internal coordinates showed a low eigen-value (1.3982892e−05), which also signifies the stability of molecular docking. Finally, the vaccine components were adopted for reverse transcription and codon optimization in E. coli strain K12 for the pGEX-4T1 vector, which supports in silico cloning of the vaccine components against the pathogen. The study directs the experimental study for therapeutics molecules discovery and vaccine candidate development with higher reliability. • Proteome mediated therapeutic target mapping for probable drug discovery in M. leprae • Prediction of common (B-cell and T-cell) epitopes and development of multi-epitopic peptide-based vaccine against M. leprae • Structure refinement, antigenic properties assessment, physicochemical characteristics and validation of vaccine construct • Molecular interaction and dynamics study of vaccine construct and human TLR4/ MD2 protein complex [ABSTRACT FROM AUTHOR]

COVID-19 is now pandemic throughout the world. Scientist, doctors are searching for effective therapy of this diseases. The remdesivir, an antiviral drug, is appeared as 'molecule of hope' for the treatment of this disease. USFDA gave emergency approval to this drug for the treatment of COVID-19. The molecular mechanism is unknown. In this paper, we tried to describe the probable molecular mechanism of remdesivir to inhibit the RNA synthesis of SARS-CoV-2. However, more detail mechanism is needed to understand mechanism of action of remdesivir. [ABSTRACT FROM AUTHOR]

Abstract: Recently, it has been suggested that anesthetic agents may have neuroprotective potency. The notion that anesthetic agents can offer neuroprotection remains controversial. Propofol, which is a short-acting intravenous anesthetic agent, may have potential as a neuroprotective agent. In this study, we tried to determine whether propofol affected the viability of human neuroblastoma SH-SY5Y cells by using the MTT assay. Surprisingly, our results showed that propofol at a dose of 1–10μM could improve cell proliferation. However, at higher doses (200μM), propofol appears to be cytotoxic. On the other hand, propofol could up-regulate the expression of key proteins involved in neuroprotection including B-cell lymphoma 2 at a dose range of 1–10μM, activation of phospho-serine/threonine protein kinase at a dose range of 0.5–10μM, and activation of phospho-extracellular signal-regulated kinases at a dose range of 5–10μM. Similarly, we demonstrate that propofol (10μM) could elevate protein levels of heat shock protein 90 and heat shock protein 70. Therefore, we choose to utilize a 10μM concentration of propofol to assess neuroprotective activities in our studies. In the following experiments, we used dynorphin A to generate cytotoxic effects on SH-SY5Y cells. Our data indicate that propofol (10μM) could inhibit the cytotoxicity in SH-SY5Y cells induced by dynorphin A. Furthermore, propofol (10μM) could decrease the expression of the p-P38 protein as well. These data together suggest that propofol may have the potential to act as a neuroprotective agent against various neurologic diseases. However, further delineation of the precise neuroprotective effects of propofol will need to be examined. [Copyright &y& Elsevier]

The devastating outbreak of COVID-19 has spread all over the world and has become a global health concern. There is no specific therapeutics to encounter the COVID-19. Small interfering RNA (siRNA)-based therapy is an efficient strategy to control human viral infections employing post-transcriptional gene silencing (PTGS) through neutralizing target complementary mRNA. RNA-dependent RNA polymerase (RdRp) encoded by the viral RdRp gene as a part of the replication-transcription complex can be adopted as an acceptable target for controlling SARS-CoV-2 mediated infection. Therefore, in the current study, accessible siRNA designing tools, including significant algorithms and parameters, were rationally used to design the candidate siRNAs against SARS-COV-2 encoded RdRp. The designed siRNA molecules possessed adequate nucleotide-based and other features for potent gene silencing. The targets of the designed siRNAs revealed no significant matches within the whole human genome, ruling out any possibilities for off-target silencing by the siRNAs. Characterization with different potential parameters of efficacy allowed selecting the finest siRNA among all the designed siRNA molecules. Further, validation assessment and target site accessibility prediction also rationalized the suitability of this siRNA molecule. Molecular docking study between the selected siRNA molecule and component of RNA interference (RNAi) pathway gave an excellent outcome. Molecular dynamics of two complexes: siRNA and argonaute complex, guide RNA, and target protein complex, have shown structural stability of these proteins. Therefore, the designed siRNA molecule might act as an effective therapeutic agent against the SARS-CoV-2 at the genome level and can prevent further outbreaks of COVID-19 in humans. • Designed siRNAs can contribute as effective therapeutic agent against SARS-CoV-2. • Target specific designing of siRNAs for post-transcriptional gene silencing of SARS-CoV-2 RdRp gene • Molecular interaction and dynamics analysis of siRNA‑argonaute protein docked complex using bioinformatics tools • Computational validation of designed siRNA off-target silencing possibilities within the whole human genome [ABSTRACT FROM AUTHOR]

The coronavirus (CoV) spike (S) protein is critical for receptor binding, membrane fusion and internalization of the virus into the human cells. We have tried to search the epitopic component of the S-protein that might be served as crucial targets for the vaccine development and also tried to understand the molecular mechanism of epitopes and TLR4/MD-2 complex for adaptive immunity. Here we identified the antigenicity and the epitopic divergence of S-protein via immunoinformatics approach. The study was performed to identify the epitopes, composition of amino acids and its distribution in epitopic regions, composition of amino acid between the identified epitopes, secondary structure architecture of epitopes, physicochemical and biochemical parameters and molecular interaction between the identified epitope and TLR4/MD-2 complex. The SARS-CoV-2 can be possibly recognised by TLR4 of host immune cells that are responsible for the adaptive immune response. We identified four SARS-CoV-2 S-protein 9mer antigenic epitopes and observed that they bind with the TLR4/MD-2 complex by varied stable molecular bonding interactions. Molecular interaction between these characterized epitopes with TLR4/MD-2 complex might be indicated the binding affinity and downstream signalling of adaptive immune response. Different physicochemical and biochemical parameters such as O-glycosylation and N-glycosylation, Hydrophobicity, GRAVY were identified within epitopic regions of S-protein. These parameters help to understand the protein-protein interaction between epitopes and TLR4/MD-2 complex. The study also revealed different epitopic binding pockets of TLR4/MD-2 complex. The identified epitopes impart suitable prospects for the development of novel peptide-based epitopic vaccine for the control of COVID-19 infection. • Identification and characterization of antigenic multi-epitopic region of SARS-CoV-2 Spike (S) protein. • Molecular interaction study of SARS-CoV-2 S-protein epitopes and human TLR4/MD-2 complex through molecular docking. • Binding with TLR4/MD-2 complex with four identified epitopes from SARS-CoV-2 S-protein might induce an immune response. • Identified epitopes (both B and T-cells) are promising candidates for epitope-based peptide-vaccine against COVID-19. [ABSTRACT FROM AUTHOR]

Gram-negative bacteria are among the causative microorganisms for zoonotic diseases in humans and teleosts. Outer membrane proteins (Omps) of Aeromonas hydrophila , a gram-negative bacterium, are critical for the subcellular integration to eukaryotic cell that can modulate the functions of macrophages. Hence Omps are recognized as immune markers for the vaccine development. In the present study, a 3-D model of Omps was identified using in silico technique and recognized through the Swiss model web-server and confirmed with Procheck and ProSA server.. The B-cell binding sites of the protein were selected from sequence alignment.. Further, the identification of B-cell epitope was carried out using modules of BCpred server (i.e. , BCPred and Amino Acid Pairs). The identified antigenic amino acid sequences for B-cells were used to determine the T-cell epitope (both MHC I & II allelic binding sequences) using ProPred 1 and ProPred servers. The epitopic regions (9 mer: LAGKTTNES and GFDGSQYGK) in the Omps that are bound together with the MHC molecules (MHC-I & II), and have maximum possible numbers of MHC alleles are recognized. It was observed that Omps of A. hydrophila are conserved across the serotypes and are immunogenic. These epitopes can stimulate significant immune responses and can be advantageous while preparing peptide-based vaccines against A. hydrophila infections. Thus, suggesting the use of Omps in the development of vaccines and immunotherapeutics against the bacterial diseases in humans and teleosts. • Outer membrane proteins characterization and modeling of Aeromonas hydrophila. • In silico modeling and validation of targeted epitopic sequences using advanced computations servers. • Determination of common antigenic regions for both B cell and T cell epitopes for novel vaccine development. • Protein docking analysis with respect to the selected MCH molecules of human and teleosts. [ABSTRACT FROM AUTHOR]