Summary: Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) enters the host cell by binding to angiotensin‐converting enzyme 2 (ACE2) receptor. Other important proteins involved in this process include disintegrin and metalloproteinase domain‐containing protein 17 (ADAM17) also known as tumour necrosis factor‐α‐converting enzyme and transmembrane serine protease 2. ACE2 converts angiotensin II (Ang II) to angiotensin (1–7), to balance the renin angiotensin system. Membrane‐bound ACE2 ectodomain shedding is mediated by ADAM17 upon viral spike binding, Ang II overproduction and in several diseases. The shed soluble ACE2 (sACE2) retains its catalytic activity, but its precise role in viral entry is still unclear. Therapeutic sACE2 is claimed to exert dual effects; reduction of excess Ang II and blocking viral entry by masking the spike protein. Nevertheless, the paradox is why SARS‐CoV‐2 comorbid patients struggle to attain such benefit in viral infection despite having a high amount of sACE2. In this review, we discuss the possible detrimental role of sACE2 and speculate on a series of events where protease primed or non‐primed virus–sACE2 complex might enter the host cell. As extracellular virus can bind many sACE2 molecules, sACE2 level could be reduced drastically upon endocytosis by the host cell. A consequential rapid rise in Ang II level could potentially aggravate disease severity through Ang II‐angiotensin II receptor type 1 (AT1R) axis in comorbid patients. Hence, monitoring sACE2 and Ang II level in coronavirus disease 2019 comorbid patients are crucial to ensure safe and efficient intervention using therapeutic sACE2 and vaccines.

The impact of COVID-19 infection on individuals with small cell lung cancer (SCLC) poses a serious threat. Unfortunately, the molecular basis of this severe comorbidity has yet to be elucidated. The present study addresses this gap utilizing publicly available omics data of COVID-19 and SCLC to explore the key molecules and associated pathways involved in the convergence of these diseases. Findings revealed 402 genes, that exhibited differential expression patterns in SCLC patients and also play a pivotal role in COVID-19 pathogenesis. Subsequent functional enrichment analyses identified relevant ontologies and pathways that are significantly associated with these genes, revealing important insights into their potential biological, molecular and cellular functions. The protein-protein interaction network, constructed under four combinatorial topological assessments, highlighted SMAD3, CAV1, PIK3R1, and FN1 as the primary components to this comorbidity. Our results suggest that these components significantly regulate this cross-talk triggering the PI3K-AKT and TGF-beta signaling pathways. Lastly, this study made a multi-step computational attempt and identified corylifol A and ginkgetin from natural sources that can potentially inhibit these components. Therefore, the outcomes of this study offer novel perspectives on the common molecular mechanisms underlying SCLC and COVID-19 and present future opportunities for drug development. [GRAPHICS] .

A metabolic network of energy-sensing molecular pathways drives the biological ageing process. Regulating certain network elements can help decelerate the ageing process and ameliorate ageing associated disorders. Bioactive phytopeptides are a prospective avenue for anti-ageing therapeutics and rejuvenation biotechnology. The present study investigates the potential of therapeutic plant peptides against cellular senescence by targeting three key proteins in the ageing network – target of rapamycin (mTOR), adenosine monophosphate-activated protein kinase (AMPK) and sirtuin 1 (SIRT1). This investigation screened a library of reported bioactive peptides using standard cheminformatic methods including in-silico ADMET, molecular docking, molecular dynamics simulation and molecular mechanics calculation. The retrieved simulation data predict 25 diverse phytopeptides as potential safe and drug-like anti-ageing biologics with half-lives >20 h and bioavailability scores >0.40. The best docked peptide, Cycloleonuripeptide B, exhibited strong binding affinity and stable complex formation with mTOR (-17.5 kCal/mol), SIRT1 (-28.54 kCal/mol) and two active sites in AMPK (-41.8 kCal/mol; −36.0 kCal/mol) during molecular dynamics simulations. The computational study acts as a foundation for future laboratory and clinical research into the potential of repurposing therapeutic phytopeptides against cellular senescence and associated pathophysiology. Communicated by Ramaswamy H. Sarma Graphical Abstract

Background: COVID-19 is transmitting worldwide drastically and infected nearly two and half million of people so far. Till date 2144 cases of COVID-19 is confirmed in Bangladesh till 18 ^th April though the stage-3/4 transmission is not validated yet. Methods: To project the final infection numbers in Bangladesh we used the SIR mathematical model. Confirmed cases of infection data were obtained from Institute of Epidemiology, Disease Control and Research (IEDCR) of Bangladesh Results: The confirmed cases in Bangladesh follow our SIR model prediction cases. By the end of April the predicted cases of infection will be 17450 to 21616 depending on the control strategies. Due to large population and socio-economic characteristics, we assumed 60% social distancing and lockdown can be possible. Assuming that, the predicated final size of infections will be 3782558 on the 92th day from the first infections and steadily decrease to zero infection after 193 days Conclusion: To estimate the impact of social distancing we assumed eight different scenarios, the predicted results confirmed the positive impact of this type of control strategies suggesting that by strict social distancing and lockdown, COVID-19 infection can be under control and then the infection cases will steadily decrease down to zero.

Throughout history, the human race has often faced pandemics with substantial numbers of fatalities. As the COVID-19 pandemic has now affected the whole planet, even countries with moderate to strong healthcare support and expenditure have struggled to contain disease transmission and casualties. Countries affected by COVID-19 have different demographics, socioeconomic, and lifestyle health indicators. In this context, it is important to find out to what extent these parametric variations are modulating disease outcomes. To answer this, this study selected demographic, socioeconomic, and health indicators e.g., population density, percentage of the urban population, median age, health expenditure per capita, obesity, diabetes prevalence, alcohol intake, tobacco use, case fatality of non-communicable diseases (NCDs) as independent variables. Countries were grouped according to these variables and influence on dependent variables e.g., COVID-19 positive tests, case fatality, and case recovery rates were statistically analyzed. The results suggested that countries with variable median age had a significantly different outcome on positive test rate (P < 0.01). Both the median age (P = 0.0397) and health expenditure per capita (P = 0.0041) showed a positive relation with case recovery. An increasing number of tests per 100 K of the population showed a positive and negative relationship with the number of positives per 100 K population (P = 0.0001) and the percentage of positive tests (P < 0.0001), respectively. Alcohol intake per capita in liter (P = 0.0046), diabetes prevalence (P = 0.0389), and NCDs mortalities (P = 0.0477) also showed a statistical relation to the case fatality rate. Further analysis revealed that countries with high healthcare expenditure along with high median age and increased urban population showed more case fatality but also had a better recovery rate. Investment in the health sector alone is insufficient in controlling the severity of the pandemic. Intelligent and sustainable healthcare both in urban and rural settings and healthy lifestyle acquired immunity may reduce disease transmission and comorbidity induced fatalities, respectively.