In silico prediction of COVID-19 cytokine storm in lung cancer types.

Lung cancer is one of the most frequently diagnosed malignant tumors and the leading cause of cancer-related death worldwide. Mainly, Non-small-cell lung cancer (NSCLC), which accounts for more than eighty-five percent of all lung cancers, consists of two major subtypes: lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC). Novel coronavirus disease (COVID-19) affected millions of people caused by acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) around the globe. Lung cancer patients and COVID-19 present unique and unfortunate lethal combinations because the lungs are the primary target organ of SARS-CoV-2 infection. Clinical studies have demonstrated that an over-activated inflammatory response associated with severe COVID-19 cases is characterized by excessive auto-amplifying cytokine release, which is defined as a "cytokine storm." ACE2 and TMPRSS2 receptors play an essential role in SARS-CoV-2 infection; therefore, using in silico analysis, we did correlation analysis with immune infiltration markers in LUAD and LUSC patient groups. Our study identified a promising correlation between immune-modulators and receptor proteins (ACE-2 and TMPRSS2), creating a domain that requires further laboratory studies for clinical authentication.

Phycochemistry and bioactivity of cyanobacterial secondary metabolites.

Microbes are a huge contributor to people's health around the world since they produce a lot of beneficial secondary metabolites. Cyanobacteria are photosynthetic prokaryotic bacteria cosmopolitan in nature. Adaptability of cyanobacteria to wide spectrum of environment can be contributed to the production of various secondary metabolites which are also therapeutic in nature. As a result, they are a good option for the development of medicinal molecules. These metabolites could be interesting COVID-19 therapeutic options because the majority of these compounds have demonstrated substantial pharmacological actions, such as neurotoxicity, cytotoxicity, and antiviral activity against HCMV, HSV-1, HHV-6, and HIV-1. They have been reported to produce a single metabolite active against wide spectrum of microbes like Fischerella ambigua produces ambigols active against bacteria, fungi and protozoa. Similarly, Moorea producens produces malygomides O and P, majusculamide C and somocystinamide which are active against bacteria, fungi and tumour cells, respectively. In addition to the above, Moorea sp. produce apratoxin A and dolastatin 15 possessing anti cancerous activity but unfortunately till date only brentuximab vedotin (trade name Adcetris), a medication derived from marine peptides, for the treatment of Hodgkin lymphoma and anaplastic large cell lymphoma has been approved by FDA. However, several publications have effectively described and categorised cyanobacterial medicines based on their biological action. In present review, an effort is made to categorize cyanobacterial metabolites on the basis of their phycochemistry. The goal of this review is to categorise cyanobacterial metabolites based on their chemical functional group, which has yet to be described.

Computational exploration of the dual role of the phytochemical fortunellin: Antiviral activities against SARS-CoV-2 and immunomodulatory abilities against the host.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections generate approximately one million virions per day, and the majority of available antivirals are ineffective against it due to the virus's inherent genetic mutability. This necessitates the investigation of concurrent inhibition of multiple SARS-CoV-2 targets. We show that fortunellin (acacetin 7-O-neohesperidoside), a phytochemical, is a promising candidate for preventing and treating coronavirus disease (COVID-19) by targeting multiple key viral target proteins. Fortunellin supports protective immunity while inhibiting pro-inflammatory cytokines and apoptosis pathways and protecting against tissue damage. Fortunellin is a phytochemical found in Gojihwadi kwath, an Indian traditional Ayurvedic formulation with an antiviral activity that is effective in COVID-19 patients. The mechanistic action of its antiviral activity, however, is unknown. The current study comprehensively evaluates the potential therapeutic mechanisms of fortunellin in preventing and treating COVID-19. We have used molecular docking, molecular dynamics simulations, free-energy calculations, host target mining of fortunellin, gene ontology enrichment, pathway analyses, and protein-protein interaction analysis. We discovered that fortunellin reliably binds to key targets that are necessary for viral replication, growth, invasion, and infectivity including Nucleocapsid (N-CTD) (-54.62 kcal/mol), Replicase-monomer at NSP-8 binding site (-34.48 kcal/mol), Replicase-dimer interface (-31.29 kcal/mol), Helicase (-30.02 kcal/mol), Papain-like-protease (-28.12 kcal/mol), 2'-O-methyltransferase (-23.17 kcal/mol), Main-protease (-21.63 kcal/mol), Replicase-monomer at dimer interface (-22.04 kcal/mol), RNA-dependent-RNA-polymerase (-19.98 kcal/mol), Nucleocapsid-NTD (-16.92 kcal/mol), and Endoribonuclease (-16.81 kcal/mol). Furthermore, we identify and evaluate the potential human targets of fortunellin and its effect on the SARS-CoV-2 infected tissues, including normal-human-bronchial-epithelium (NHBE) and lung cells and organoids such as pancreatic, colon, liver, and cornea using a network pharmacology approach. Thus, our findings indicate that fortunellin has a dual role; multi-target antiviral activities against SARS-CoV-2 and immunomodulatory capabilities against the host.

Single-Cell Transcriptome Analysis Reveals the Role of Pancreatic Secretome in COVID-19 Associated Multi-organ Dysfunctions.

The SARS-CoV-2 infection affects the lungs, heart, kidney, intestine, olfactory epithelia, liver, and pancreas and brings forward multi-organ dysfunctions (MODs). However, mechanistic details of SARS-CoV-2-induced MODs are unclear. Here, we have investigated the role of pancreatic secretory proteins to mechanistically link COVID-19 with MODs using single-cell transcriptome analysis. Secretory proteins were identified using the Human Protein Atlas. Gene ontology, pathway, and disease enrichment analyses were used to highlight the role of upregulated pancreatic secretory proteins (secretome). We show that SARS-CoV-2 infection shifts the expression profile of pancreatic endocrine cells to acinar and ductal cell-specific profiles, resulting in increased expression of acinar and ductal cell-specific genes. Among all the secretory proteins, the upregulated expression of IL1B, AGT, ALB, SPP1, CRP, SERPINA1, C3, TFRC, TNFSF10, and MIF was mainly associated with disease of diverse organs. Extensive literature and experimental evidence are used to validate the association of the upregulated pancreatic secretome with the coagulation cascade, complement activation, renin-angiotensinogen system dysregulation, endothelial cell injury and thrombosis, immune system dysregulation, and fibrosis. Our finding suggests the influence of an upregulated secretome on multi-organ systems such as nervous, cardiovascular, immune, digestive, and urogenital systems. Our study provides evidence that an upregulated pancreatic secretome is a possible cause of SARS-CoV-2-induced MODs. This finding may have a significant impact on the clinical setting regarding the prevention of SARS-CoV-2-induced MODs.

Urban air pollution reduction: evidence from phase-wise analysis of COVID-19 pandemic lockdown

Until 31 May 2020, more than six million confirm COVID-19 cases had been reported worldwide. Lockdown has resulted in significant air quality improvement, especially in urban regions. The lockdown has acted as a natural experiment empowering researchers, policymakers, and governing bodies. The present study focuses on quantifying and analysing the effect of lockdown on India’s metropolitan cities, namely New Delhi, Mumbai, Kolkata, Chennai, and Bangalore. The study analyses the phase-wise and diurnal variations in the air quality from 24 March 2020 to 31 May 2020 while focussing on-peak and off-peak duration concentrations. To investigate the reason behind pollutant reduction, correlation of drop percentages in pollutant concentrations with vehicle population, extent of construction activity, and meteorological parameters are analysed. The 24-h drop in PM10 and PM2.5 showed a high correlation (R2 = 0.97 and 0.72, respectively) with the city’s vehicle population. During peak hours, the inland cities (Delhi and Bangalore), with a more extensive vehicle fleet, recorded a higher drop in PM10 and PM2.5 concentrations than coastal cities (Mumbai, Chennai, and Kolkata). With respect to 2019 concentration, the maximum decrease in pollutant concentrations averaged across the five study locations was recorded in NO2 (46%), followed by PM2.5 (40%), PM10 (37%), and CO (19%). SO2 and O3 contrarily recorded an overall increase of 40% and 41%. These results wherein vehicular pollutants recorded the maximum drop indicate that reduced vehicular traffic primarily influenced air quality improvement during the lockdown.

Aerosol number concentrations and new particle formation events over a polluted megacity during the COVID-19 lockdown

The present study investigates the particle number concentrations and size distributions in the ultrafine and fine-sized regimes over a polluted megacity, New Delhi (28.75° N, 77.12° E), India. The experiments were conducted during the periods (April-May 2020) of strict social and travel restrictions (lockdown) imposed by the Government of India aiming to contain the spread of Coronavirus Disease 19 (COVID-19) pandemic. The different phases of the COVID-19 lockdown witnessed restrictions of varying magnitudes with the significant cessation of anthropogenic sources, viz., industrial, road, railways, and air traffic emissions. Using this unique opportunity, the impact of varying urban emissions on particle number size distributions and new particle formation events were examined. The mean total number concentrations were in the range of ∼ (2 to 3.5) x 104 cm-3 and depicted a gradual increase (∼26%) with progressive unlock of the anthropogenic activities. At the same time, accumulation particle concentrations were doubled. However, ultrafine particles (UFP) (diameter < 100 nm) dominated (50-88%) the total number concentrations during most of the days and several new particle formation (NPF) events resulting in elevated (2 - 5 fold) UFP concentrations were observed. Subsequently, the particles grew to larger sizes with rates ∼3.31- 8.37 nm hr-1. The NPF events occurred during the daytime, and during the events, a clear enhancement in the concentrations of [H2SO4] proxy (2 to 3.5 x 107 molecules cm-3;2-3 orders higher than the non-event values) suggesting the role of strong gas-phase photochemistry. Also, some of the NPF events were associated with increased odd oxygen concentrations [Ox = O3+NO2], indicating the regional nature of the precursors and participation of VOC precursors in nucleation/growth. Interestingly, different classes of NPF events were seen during the strictest lockdown period, whereas more frequent and well-defined NPF events were witnessed when anthropogenic activities were opened up with conditional relaxations. These events demonstrated the competition between source strengths of precursor vapors from anthropogenic activities and primary particles acting as condensation sink restricting NPF. This study highlighted that urban pollution mitigation policies need to consider ultrafine particles emanating from the secondary aerosol formation process from traffic emissions.

Saponins: Extraction, bio-medicinal properties and way forward to anti-viral representatives.

Medicinal or herbal plants are widely used for their many favourable properties and are generally safe without any side effects. Saponins are sugar conjugated natural compounds which possess a multitude of biological activities such as medicinal properties, antimicrobial activity, antiviral activity, etc. Saponin production is a part of the normal growth and development process in a lot of plants and plant extracts such as liquorice and ginseng which are exploited as potential drug sources. Herbal compounds have shown a great potential against a wide variety of infectious agents, including viruses such as the SARS-CoV; these are all-natural products and do not show any adverse side effects. This article reviews the various aspects of saponin biosynthesis and extraction, the need for their integration into more mainstream medicinal therapies and how they could be potentially useful in treating viral diseases such as COVID-19, HIV, HSV, rotavirus etc. The literature presents a close review on the saponin efficacy in targeting mentioned viral diseases that occupy a high mortality rate worldwide. This manuscript indicates the role of saponins as a source of dynamic plant based anti-viral remedies and their various methods for extraction from different sources.

Incidence and pattern of dental emergencies and their management during Covid-19 pandemic : An experience of Nepali dentists working during lock down

Introduction: Corona Virus Disease-2019 (COVID-19) is highly contagious nature of disease which has spread all over the world in short span of time leading to significant number of death. WHO has declared pandemic and every nation is fighting with their all possible resources to control this disease. The impact of COVID-19 in dentistry is enormous. Most of the dental hospitals and clinic are providing emergency dental services only. So the aim of this research is to find out the nature of dental emergency during the initial month of lock down in Nepal. Additionally this research will try to find out the number of dental emergencies as well as perception of dentists on impact of COVID-19 on dentistry. Materials and Method : A set of electronic questionnaires were sent to 150 Nepal Medical Council registered Nepalese dentists out of which only 122 dentists responded. A consent was obtained prior to collecting data for research purpose. All the quantitative answers were recorded in SPSS spread sheet where as qualitative data were collected in Microsoft word. Descriptive statistics were applied to explain the responses whenever applicable. Result: Out of 122 respondents, maximum were from province 3 and 4 (50% and 34%). Almost half of the respondents were general dental practioners and similar percentage of respondents were working at dental/medical colleges and government centers. 90% of the doctors had consulted patients during lock down period. Average 5-20 cases were seen during the lock down by majority of doctors. Nearly 58% of the doctors had done only virtual consultation and most common emergency was dental pain(n= 92) and swelling( n= 37). Majority of the respondents thought that standard of dental disinfection and sterilization will increase after pandemic, however most of the dentists thought they will be using PPE for dental work and cost of dental treatment will be increased because of the added cost of extra precaution. 90% of the dentists believed that they are going to change the way they practice dentistry after they reopen their clinic. Conclusion: The most common type of dental emergency during lock down is dental pain ,swelling, dento-maxillofacial trauma and broken orthodontic appliances. Virtual dental consultation is gaining popularity among dentists in Nepal and Nepalese dentists are going to change the way of dental practice because of COVID-19.

SARS-CoV-2 cell receptor gene ACE2 -mediated immunomodulation in breast cancer subtypes.

The recent outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has impacted the world severely. The binding of the SARS-CoV-2 virus to the angiotensin-converting enzyme 2 (ACE2) and its intake by the host cell is a necessary step for infection. ACE2 has garnered widespread therapeutic possibility as it is entry/interactive point for SARS-CoV-2, responsible for coronavirus disease 2019 (COVID-19) pandemic and providing a critical regulator for immune modulation in various disease. Patients with suffering from cancer always being on the verge of being immune compromised therefore gaining knowledge about how SARS-CoV-2 viruses affecting immune cells in human cancers will provides us new opportunities for preventing or treating virus-associated cancers. Despite COVID-19 pandemic got center stage at present time, however very little research being explores, which increase our knowledge in context with how SARS-CoV-2 infection affect cancer a cellular level. Therefore, in light of the ACE-2 as an important contributor of COVID-19 global, we analyzed correlation between ACE2 and tumor immune infiltration (TIL) level and the type markers of immune cells were investigated in breast cancer subtypes by using TIMER database. Our findings shed light on the immunomodulatory role of ACE2 in the luminal A subtype which may play crucial role in imparting therapeutic resistance in this cancer subtype.

Comparative study on air quality status in Indian and Chinese cities before and during the COVID-19 lockdown period.

Amidst COVID-19 pandemic, extreme steps have been taken by countries globally. Lockdown enforcement has emerged as one of the mitigating measures to reduce the community spread of the virus. With a reduction in major anthropogenic activities, a visible improvement in air quality has been recorded in urban centres. Hazardous air quality in countries like India and China leads to high mortality rates from cardiovascular diseases. The present article deals with 6 megacities in India and 6 cities in Hubei province, China, where strict lockdown measures were imposed. The real-time concentration of PM2.5 and NO2 were recorded at different monitoring stations in the cities for 3 months, i.e. January, February, and March for China and February, March, and April for India. The concentration data is converted into AQI according to US EPA parameters and the monthly and weekly averages are calculated for all the cities. Cities in China and India after 1 week of lockdown recorded an average drop in AQIPM2.5 and AQINO2 of 11.32% and 48.61% and 20.21% and 59.26%, respectively. The results indicate that the drop in AQINO2 was instantaneous as compared with the gradual drop in AQIPM2.5. The lockdown in China and India led to a final drop in AQIPM2.5 of 45.25% and 64.65% and in AQINO2 of 37.42% and 65.80%, respectively. This study will assist the policymakers in devising a pathway to curb down air pollutant concentration in various urban cities by utilising the benchmark levels of air pollution.