ABSTRACT
Introduction Entry factors angiotensin converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) facilitate Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) entry into the host cells. Despite SARS-CoV-2s preference for respiratory system, extra-pulmonary organ involvement has been suggested. Recent studies report that SARS-CoV-2 leads to direct hepatic impairment in COVID-19 patients, necessitating further investigations about hepatic involvement. ACE2 and TMPRSS2 are expressed in primary human hepatocytes (PHH), suggesting a possible susceptibility to SARS-CoV-2. Despite this, data on infection and factors modulating functional regulation of SARS-CoV-2 infection in PHH are lacking. MicroRNAs (miRNAs) are approximately 22 nucleotide-long non-coding RNAs that have been shown to regulate various cellular processes including virus-host interactions. We aimed to study the susceptibility of PHH to SARS-CoV-2 and to evaluate the potential of miRNAs in modulating viral infection. Materials and methods We investigated the role of miRNAs to regulate SARS-CoV-2 infection in PHH in vitro. To strengthen our fndings, we analysed liver autopsies from COVID-19 patients. Results We demonstrate that PHH can be readily infected with SARS-CoV-2, resulting in robust replication and sustained host responses as indicated by the upregulation of several interferon-stimulated genes. In silico analyses unravelled miR-200c-3p, miR-429 and miR-141-3p as candidate miRNAs targeting ACE2 and, let-7c-5p targeting TMPRSS2. Expression of these miRNAs reduced SARS-CoV-2 infection in PHH. Furthermore, expression of several endogenous miRNAs was altered upon SARS-CoV-2 infection in PHH and human liver autopsies. Conclusion Our results show that PHH are susceptible towards SARS-CoV-2 and cellular miRNAs can diminish SARS-CoV-2 viral burden.
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PVP-K30 is an powerful binder for effervescent tablet and can be used each in moist granulation and in direct compression low relative humidity (maximum 25% or much less) and moderate to cool temperatures (25°C ) Inside the production regions are essential to save you granules or tablet from sticking, picking up moisture in the air which might also cause product degradation.1,2 The patient must take vitamin c supplement at the same time to will increase immunity and minimized the disease burden. The aim of this observe turned into to design broaden and evaluation of the effervescent tablet which comprise zinc gluconate and ascorbic acid (vitamin c aggregate.3,4 2. [...]the tablet had been dried in an oven with air move at 50°C for 1 hour after which packed in plastic tubes after cooling.5,6 Wet Granulation: According to table 1 mixture of sodium bicarbonate, citric acid passed through 35 mesh sieve much (< 0.5 mm) and mixed for 10 minutes. then 5% w/v PVP-K30 solution is isopropanol changed into added dropwise the usage of a pipette to the combination until an pasty mass formed. Were kept under compatibility study for temperature 400C. ±75 RH for period of two weeks. without any significant physical changes. [...]it is confirmed that all the active and inactive excipients which were kept under compatibility study are compatible with each other all these ingredients were selected and used in present work.9,10 Discussion: The IR spectrum of the Zinc gluconate was recorded and the IR spectra of zinc gluconate show functional group as per the structure.
ABSTRACT
Infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the current coronavirus disease 2019 (COVID-19) pandemic. Despite a preferential respiratory tropism of SARS-CoV-2, multi-organ involvement has been described. SARS-CoV-2 entry into host cells is mediated by the entry factors angiotensin converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2). Recent studies suggest that SARS-CoV-2 causes direct hepatic impairment in COVID-19 patients. Interestingly, ACE2 and TMPRSS2 are also expressed in primary human hepatocytes (PHH). Despite this evidence, data on infection and factors modulating functional regulation of SARS-CoV-2 infection in PHHs are scarce. MicroRNAs (miRNAs) are a class of small non-coding RNAs that have been described to modulate various cellular processes and have been implicated as potential therapeutic target. We aimed to study the infection of PHHs with SARS-CoV-2 and to evaluate the potential of miRNAs for modulating viral infection. We could demonstrate that PHHs can be readily infected with SARS-CoV-2. Bioinformatics analyses revealed miR- 200c-3p, miR-429, let-7c-5p and miR-141-3p as candidate miRNAs targeting ACE2 and TMPRSS2. All miRNAs were able to reduce SARS-CoV-2 burden in PHH by supressing ACE2 and TMPRSS2. Our findings provide the first evidence of the applicability of miRNA molecules in reducing SARS-CoV-2 viral loads.
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Corona virus disease 2019 (COVID-19) caused by corona virus SARS-CoV-2 is believed to be originated in Wuhan province of China, which has spread all over the world. It has severely impacted the social, cultural, educational, research and development programmes throughout the globe. Since the inception of various lifeforms on planet earth, forests' plays an important role in the evolutionary history of organisms and fitness persuades the existence of modern-day species in different ecosystems. The visible effect of pandemic leads to the lockdown with positive implications on the earth biosphere as a whole; while on other hand, lockdown seized and reduced the urbanization and developmental projects, especially the research and development progress in the field of forestry and allied sciences. This viewpoint addresses key questions and point-out with detailed exploration of the problem - as how COVID-19 pandemic impacts forestry research all over the world? We also suggest possible solutions, and define the role and association of disciplines, such as bioinformatics, remote sensing and statistical modules along with previously explored and collected field data as a sustainable measure to resolve the problems of forestry sector of this mighty challenge.
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Fermented soybean products are traditionally consumed and popular in many Asian countries and the northeastern part of India. To search for potential agents for the interruption of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Spike glycoprotein 1 (S1) and human angiotensin-converting enzyme 2 (ACE2) receptor interactions, the in silico antiviral prospective of peptides identified from the proteome of kinema was investigated. Soybean was fermented using Bacillus licheniformis KN1G, Bacillus amyloliquefaciens KN2G and two different strains of Bacillus subtilis (KN2B and KN2M). The peptides were screened in silico for possible antiviral activity using two different web servers (AVPpred and meta-iAVP), and binding interactions of selected 44 peptides were further explored against the receptor-binding domain (RBD) of the S1 protein (PDB ID: 6M0J) by molecular docking using ZDOCK. The results showed that a peptide ALPEEVIQHTFNLKSQ (P13) belonging to B. licheniformis KN1G fermented kinema was able to make contacts with the binding motif of RBD by blocking specific residues designated as critical (GLN493, ASN501) in the binding of human angiotensin-converting enzyme 2 (ACE2) cell receptor. The selected peptide was also observed to have a significant affinity towards human toll like receptor 4 (TLR4)/Myeloid Differentiation factor 2 (MD2) (PDB ID: 3FXI) complex known for its essential role in cytokine storm. The energy properties of the docked complexes were analyzed through the Generalized Born model and Solvent Accessibility method (MM/GBSA) using HawkDock server. The results showed peptidyl amino acids GLU5, GLN8, PHE11, and LEU13 contributed most to P13-RBD binding. Similarly, ARG90, PHE121, LEU61, PHE126, and ILE94 were appeared to be significant in P13-TLR4/MD2 complex. The findings of the study suggest that the peptides from fermented soy prepared using B. licheniformis KN1G have better potential to be used as antiviral agents. The specific peptide ALPEEVIQHTFNLKSQ could be synthesized and used in combination with experimental studies to validate its effect on SARS-CoV-2-hACE2 interaction and modulation of TLR4 activity. Subsequently, the protein hydrolysate comprising these peptides could be used as prophylaxis against viral diseases, including COVID-19.
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BACKGROUND: Epilepsy is one of the most common problems in neurology clinical practice and currently we are in the midst of the coronavirus outbreak. The coronavirus pandemic is an epidemiological and psychological crisis, which is likely to affect persons with epilepsy. OBJECTIVES: This study was designed to evaluate the impact of COVID-19 pandemic on patients with epilepsy and effects on their mental health. MATERIALS AND METHODS: This was a cross-sectional web-based survey carried out at the department of Neurology at a tertiary care hospital. A questionnaire was designed in the local language using Google Forms to assess basic knowledge regarding epilepsy, coronavirus, effects of COVID-19 and lockdown on epileptic patients and also effects on their mental health. The link to the online survey was distributed via WhatsApp messenger to epilepsy patients. RESULTS: One hundred fifty-six cases were enrolled with 69.1% were below 34 years of age and male: female ratio was 1.2:1. Only 34.3% of the participants were employed and 50% of patients had an income of less than Rs. 3000 per month. Of the patients enrolled, 20.5% reported the "devil" and superstitions as a cause of epilepsy and only 10% of patients thought that tantric (holy priest) could treat the disease better than doctors. 53.8% of patients worried about getting COVID-19 and could not stop thoughts about being infected by coronavirus bothering them. 30.3% patients had increased seizure frequency during COVID-19 pandemic, of which the most common reason was that they forgot to take regular antiepileptic drugs (22.7%) or they had faced difficulty in obtaining medicine due to lockdown (12.1%). During the pandemic, 17% of patients reported depression symptoms and another 21% reported anxiety symptoms. CONCLUSION: The current COVID-19 pandemic negatively affected patients with epilepsy and increased seizure frequency, depression, anxiety, unemployment, and financial difficulty in obtaining medication.